Study Guide

Department of Biochemistry, Genetics & Microbiology

Division of Genetics

Faculty of Natural and Agricultural Sciences

Genetics in Human Health

GTS 368

2021
Table of Contents
1. INTRODUCTION .............................................................................................................. 1
1.1 WELCOME ............................................................................................................................ 1
1.2 EDUCATIONAL APPROACH ................................................................................................... 1
1.3 RESPONSIBILITIES OF THE STUDENT ..................................................................................... 1
1.4 ONLINE LEARNING IN RESPONSE TO THE COVID-19 NATIONAL STATE OF DISASTER ............. 2

2. MODULE ADMINISTRATION ........................................................................................... 3

2.1 CONTACT DETAILS ................................................................................................................ 3
2.2 TIMETABLE ........................................................................................................................... 4
2.3 STUDY MATERIAL AND PURCHASES ...................................................................................... 4
2.4 PROGRAMME/DEPARTMENTAL/MODULE RULES, REQUIREMENTS AND GUIDELINES ........... 5
2.5 CODE OF CONDUCT .............................................................................................................. 5

3. Module information ....................................................................................................... 6

3.1 PURPOSE OF THE MODULE ................................................................................................... 6
3.2 MODULE OUTCOMES ........................................................................................................... 7
3.3 ARTICULATION WITH OTHER MODULES IN THE PROGRAMME.............................................. 7
3.4 MODULE STRUCTURE ........................................................................................................... 8
3.5 LEARNING PRESUMED TO BE IN PLACE ............................................................................... 13
3.6 CREDIT MAP AND NOTIONAL HOURS ................................................................................. 14
3.7 STUDY UNITS...................................................................................................................... 15
4. Assessment .................................................................................................................. 29
4.1 ASSESSMENT PLAN............................................................................................................. 29
4.2 ASSESSMENT POLICY .......................................................................................................... 30
4.3 PLAGIARISM ....................................................................................................................... 31

5. Support services ........................................................................................................... 31

5.1 SAFETY IN THE EVENING AND EMERGENCIES ...................................................................... 31
5.2 E-LEARNING SUPPORT ........................................................................................................ 32
5.3 OTHER SUPPORT SERVICES ................................................................................................. 33
1. INTRODUCTION
1.1 WELCOME
Welcome to GTS368 - this course introduces you to the principles of molecular genetics as they
apply to human health and disease – also known as molecular or genomic medicine. There has
been an explosion of knowledge concerning the role that genetics play in human health from the
moment of conception to death. The advent of next generation sequencing has revolutionized
how we study genetic variation in the context of human health and disease. The aim of this
module is to give you an overview of the evolution of genetic/genomic medicine from the
identification of single genes that cause diseases to the developing vision of personalized
medicine that is informed by each person’s unique clinical, genetic, genomic, and environmental
information. We also focus on the ethical and social issues that may be raised by genetic and
genomic tests.

1.2 EDUCATIONAL APPROACH

“The overall teaching policy of the University of Pretoria (UP) makes provision for an outcomes
based, learning-centred, active flexi-learning environment. This implies that students are
expected to participate actively in the learning activities.” The lectures are presented in such a
way as to facilitate learning, in other words, to explain the most important and difficult aspects
of the work and to help the student get an overview of the topic.

1.3 RESPONSIBILITIES OF THE STUDENT

1.3.1 How to study (and succeed)

You must make a substantial time commitment to this course. There is time spent in lectures and
practical sessions, but also time spent preparing for class, by reading the assigned notes/
sections, key-cases and the questions related to it, and studying for tests. Your attendance at
lectures can be either low-quality or high-quality. High-quality attendance entails being critical
during the lecture, asking questions such as: “Why does it work that way?” or “How do we know
that? What is the evidence? How does this relate to what was said the other day about…?”
These are questions showing critical thinking as opposed to questions like: “Could you repeat
that?” or “Do we have to know this for the test?”

Successful students carry out some sort of lecture follow-up activity. For many this means
rewriting their lecture notes. This may be tedious for some students – an alternative follow-up
activity is a strategy known as Concept Mapping. This is an activity that helps reorganize the
information in a way that conforms to your mental “landscape”. It helps you to discern patterns
and relationships between concepts. Concentrate on the concepts, you will not be asked to
recall picky details. You will be asked to apply broad concepts to solve specific problems. If you
know and understand all the work dealt with in class, and use the study guide as an aid to study

1
from the textbook, ClickUP and other listed sources, you will not encounter any problems in the
assessments.

It is very important to revise/work continuously throughout the semester so that you can pass
the course on your semester mark. Do not rely on the final exam to rescue a poor performance.

1.3.2 Learning Styles

You can learn more from your studies in any subject if you know something about your personal
learning preferences (your mental “landscape”). At the VARK site [https://vark-
learn.com/thevark-questionnaire/] you may take a simple, informal assessment of your learning
style. After completing the VARK learning style inventory, explore the tips for using your
preferred style to enhance learning.

1.3.3 Instructions for using the study guide

The study guide is compiled to form the backbone of the course and is consequently an essential
study aid. For every study unit the relevant study material in the textbook is indicated, key points
are summarized, followed by specific learning outcomes and self-study activities. You should be
able to address the learning outcomes and answer the self-study questions at the end of a study
unit. The learning outcomes reflect the type of questions you are likely to encounter in a test or
exam and the self-study part include some additional reading material to broaden your insight.
Both factual and conceptual knowledge will be assessed.

1.4 ONLINE LEARNING IN RESPONSE TO THE COVID-19 NATIONAL STATE OF

DISASTER
Following the announcement in March 2020 by the Presidency of a nationwide restriction on
public gatherings and a State of Disaster in response to the Coronavirus pandemic, the University
of Pretoria has resumed its teaching and learning activities through an online-only medium. We
will make exclusive use of ClickUP for the online lectures, tutorials and assessments. The online
medium will continue until the Government lifts restrictions on public gatherings and
Universities are permitted to resume contact sessions. Any revised schedules based on changes
in the State of Disaster will be communicated to students as soon as they are announced by the
University.

The lecturers will therefore provide E-lectures (either pre-recorded, or live via Blackboard
Collaborate) according to the lecture schedule in this document. We request that students
consult the pre-recorded lectures as per the roster in this document, alongside the textbook.
Similarly, we will proceed with the online implementation of tutorials. Instructions for individual
tutorials, practical tests and quizzes will be posted on ClickUP. Please find detailed information
on pages 11-12.

2
2. MODULE ADMINISTRATION
2.1 CONTACT DETAILS

Pathology building,
Dr Pontsho Moela (Academic [email protected]
Room 5-47, Prinshof Campus
Coordinator & Lecturer)
Tel: 012 420 3885
Nat & Agric Sciences building,
[email protected]
Dr Wilma Fick (Lecturer) Room 8-37, Hatfield Campus
Tel: 012 420 3255
Pathology Building
[email protected]
Dr Engela Honey (Lecturer) Room 5- 53, Prinshof Campus
Tel 012 319-2269
Nat & Agric Sciences building,
Mrs Adrene Laubscher [email protected]
Room 7-36, Hatfield Campus
(Course administrator)
Tel: 012 420 6435

MEETINGS:

• For all administrative issues (e.g. sick notes, practical exemption), please consult with the
Course Administrator Mrs Adrene Laubscher.

• Lecturers are happy to meet with students about the course theory and content. If you wish
to meet with a lecturer, please make an appointment for a meeting via email. This way, we
can assure that we have adequate time to address all of your questions. Please come for
assistance earlier, rather than later! Please don’t wait until you are really struggling and
falling behind.

Faculty Student Advisors:

Chemistry Building,
Ms Dolly Ayob [email protected]
Room 3-22.1, Hatfield Campus
Dr Erna Gerryts [email protected]
Tel: (012) 420 4990 / 2238

Your Faculty Student Advisor can advise you on goal-setting, adjustment to

university life, time management, study methods, stress management and career
exploration. Book an individual consultation or attend a workshop. For other
support services see Section 5.

3
2.2 TIMETABLE

CONTACT SESSIONS:

• LECTURES: Monday 10:30 - 11:20 Narrated PowerPoints

Wednesday 14:30 - 15:20 Narrated PowerPoints

• PRACTICALS: Tuesday 8:00 - 10:20 Online via Blackboard Collaborate

NOTE: Attendance of all practical sessions is compulsory.

Due to the online nature of the tutorials and connectivity challenges, attendance not will be
monitored during active tutorial sessions. You will however be required to submit hand written
assignments as requested and specified per tutorial. The assignment submission will be
considered as your attendance. Selected questions will be marked at the discretion of the
lecturers. These marks will contribute to the Practical mark. Failing to submit an assignment will
result in a mark of zero for that particular tutorial unless a valid excuse is submitted to Mrs
Laubscher at [email protected] within three working days after the submission date.
A valid excuse consists of either a valid medical certificate (see page 29) or proof of power cuts
or network outages over extended periods. On receipt of a valid excuse, the student will not be
exempted but arrangements will be made to submit their assignment.

Note: Tutorial exemption will not be considered in 2021

2.3 STUDY MATERIAL AND PURCHASES

The content of this module is almost exclusively based on the prescribed textbook. It is essential
that you acquire this textbook:

GENETICS AND GENOMICS IN MEDICINE (2015)

Tom Strachan, Judith Goodship & Patrick Chinnery
Garland Science, New York
ISBN 978-0-8153-4480-3
Additional study material
• PowerPoint presentations of the lectures will be made available on ClickUP.
• Journal articles and other additional information will be made available on ClickUP
• Both the practical and lecture sections of the GTS368 course can be augmented by
information from Scitable [www.nature.com/scitable/topics] - select the Genetics topic
on the web page. Scitable is a free science library and personal learning tool offered by
the Nature Publishing Group.

4
2.4 PROGRAMME/DEPARTMENTAL/MODULE RULES, REQUIREMENTS AND GUIDELINES

Please note that the following regulations apply in the Department of Biochemistry, Genetics and
Microbiology:

Ø Class attendance is compulsory; absenteeism from scheduled lectures may be seen as a failure to comply
with pass requirements (code 984). Class attendance may be accessed using a class list and/or short tests to
test the understanding of essential principles underlying gene regulation in Eukaryotes.

Ø According to University regulations, a pass grade is subject to the satisfactory completion of all required
components of the module – both theory and practical. A student will automatically be given a “do not
comply with pass requirements” (code 984) if:

• They have not attended all practical sessions and submitted all required practical assignments as
scheduled (or presented valid documentation of absence for any missed practicals and/or assignments
within 3 days);

• They have not written the officially scheduled semester test/s or the scheduled sick test.

Ø According to the regulations of the Faculty of Natural and Agricultural Sciences, students with a semester
mark below 40% are refused entrance into the exam (code 988).

Ø The final mark for the module is the average of your semester mark and examination mark. The final pass
mark for the course is 50%. Note that a subminimum of 40% for the examination paper is required.

Ø A final mark average of 40-49% is required to qualify for a supplementary exam as scheduled by the Faculty.
There will be a perusal opportunity to view your exam paper prior to the supplementary examination. A
supplementary exam comprises a new paper different from the original exam.

Ø Ancillary exams may be granted to borderline distinction candidates at the discretion of the lecturer. A
maximum of 75% can be obtained for the ancillary exam.

Ø All modules are subject to external moderation. All final year modules are moderated by an external
examiner not associated with UP.

Ø Admission to a Chancellor’s Exam is granted by the Dean’s office. As such all applications should be made via
Faculty administration.
Ø Marked test papers will not be released to students on an individual basis, but will be made available during
practical sessions, and after that from the designated area in front of room 7-36 in the Agricultural Sciences
Building.

2.5 CODE OF CONDUCT

We are not only facilitating learning in a module, we are also preparing you for the world of work.
We expect you to adhere to the code of conduct as spelled out in the Escalation policy of UP.

Communication via email

When you send an email to your lecturer, you have to use a respectful tone and include all the
following aspects:
• A clear and explanatory subject line (e.g. “Submission of sick note – P Mduli”);

5
• Your full name and surname at the end of the mail;
• Your student number;
• The module involved; and
• Short and clear message.

Compliments and complaints

You are more than welcome to express your appreciation to your lecturer or tutor and supply
feedback about aspects of the course that you enjoy and find valuable.

If you have a query or complaint, you have to submit it in writing with specifics of the issue or
the nature of the complaint. It is imperative that you follow the procedure outlined below in
order to resolve your issues:
1. consult the lecturer concerned about your complaint/concerns. If the matter has not been
resolved,
2. consult the class representative (The primary function of the Class
Representative is to serve as a two-way communication channel
between the class and the lecturer). If the matter has not been
resolved,
3. consult the academic co-ordinator (Dr Moela) If the matter has not
been resolved,
4. consult the Head of Department
If the matter has still not been resolved,
5. consult with the Dean of the Faculty (as the last resort)

Use of cell phones and other recording devices during lectures and practicals
According to the UP General Rules and Regulations, page 15, cellular phones may not be used at
all during lectures and practical sessions and must be switched off. Furthermore, students are
prohibited from recording lectures. However, in the case of students with special needs, prior
arrangements should be made to obtain the necessary approval. Students caught recording and
distributing lectures without prior approval will face disciplinary action.

3. MODULE INFORMATION

3.1 PURPOSE OF THE MODULE

There has been an explosion of knowledge concerning the role that genetics play in human
health from the moment of conception to death. The advent of next generation sequencing has
revolutionized how we study genetic variation in the context of human health and disease. The
aim of this module is to give you an overview of the evolution of genetic/genomic medicine from

6
the identification of single genes that cause diseases to the developing vision of personalized
medicine that is informed by each person’s unique clinical, genetic, genomic, and environmental
information. In addition you will be expected to have an appreciation for the ethical and social
issues that may be raised by genetic and genomic tests.

3.2 MODULE OUTCOMES

At the end of this module, you should be able to:

• Identify and solve problems by using critical and creative thinking
• Work effectively with others as a member of a team
• Organise and managing oneself and one’s activities responsibly and effectively.
• Collect, analyze, organize and critically evaluate information
• Communicate effectively using visual and language skills in the modes of oral and
written persuasion
• Use science and technology responsibly, effectively and critically

3.3 ARTICULATION WITH OTHER MODULES IN THE PROGRAMME

The prerequisites for the GTS 368 module are as follows:

v GTS251 / GTS 261 - Construction of genetic and physical genome maps, basic principles of
linkage mapping and GWAS studies. Principles of Next-Generation sequence
technologies, whole genome and exome sequencing.

Knowledge expected to be in place:

v GTS351 - Gene regulation and cancer
v GTS261 - Basic principles of gene mutation and DNA repair; single-gene inheritance
v GTS161 - Chromosome structure/number, cell cycle, mitosis and meiosis.

7
3.4 MODULE STRUCTURE

STUDY UNITS OUTLINE

SU 1: Introduction to genetics and human health .......................................... (3 lectures)

Textbook Chapters 2 & 5

(a) Human Karyotype

(b) Patterns of single-gene inheritance (Revision)
(c) Sex chromosomes and X-chromosome inactivation

SU 2: Origins of human genetic variability…………........................................... (4 lectures)

Textbook Chapters 1-3 as background of prior knowledge

(a) Origins of DNA sequence variation

(b) The scale of human genetic variation
(c) Pathogenic nucleotide substitutions and tiny insertions and deletions
(d) Moderate to large-scale pathogenic mutations by repetitive DNA

SU 3: Origins of human genetic variability and its consequences……………………. (3 lectures)

Textbook parts of Chapters 4, 5, 6 & 7
(a) Chromosome abnormalities and the effects of pathogenic variants on the
phenotype
(b) Genomic imprinting
(c) Modifier genes and environmental factors

SU 4: Identifying human disease genes & susceptibility to complex diseases………… (5 lectures)

Textbook Chapter 8
(a) Identifying genes in monogenic disorders
(b) Mapping & identifying genetic susceptibility to complex traits
(c) Gene-environment interactions and epigenetic factors

SU 5: Treatment of genetic disorders and genetic treatment of disease .................. (3 lectures)

Textbook Chapter 9
(a) Overview of treatment strategies for genetic disorders
(b) Genetic treatment of disease

8
(c) Genetic inputs into treating disease with small molecule drugs (d) Principles of
gene therapy

SU 6: Cancer genetics and genomics .............................................................. (3 lectures)

Textbook Chapter 10
(a) Fundamental characteristics & evolution of cancer
(b) Oncogenes & Tumour Suppressor genes

SU 7: Genetic testing from genes to genomes ................................................ (6 lectures)

Textbook Chapter 11
(a) Overview of genetic testing
(b) Genetic testing for chromosome abnormalities & large-scale DNA changes
(c) Genetic testing for small-scale DNA changes
(d) Prenatal screening and diagnosis

LECTURES TIMETABLE

PM: Dr Pontsho Moela WF: Dr Wilma Fick EH: Dr Engela Honey

Date Topic Lecturer Textbook
pages - study
before
lecture
1 16 Aug SU1 Basic principles: genetics and human health (1) WF p. 34-36
- Human Karyotype p213-p215,
Box 7.4,
p.441-442
2 18 Aug SU1 Basic principles: genetics and human health (2) WF p. 117-129
- Patterns of single-gene inheritance (Revision)
3 23 Aug SU1 Basic principles: genetics and human health (3) WF p. 122, 124,
- Sex chromosomes and X-chromosome inactivation p. 126-128,
p. 173-175
4 25 Aug SU2 Human genetic variability (1) PM p. 80-84
- Origins of DNA sequence variation
5 30 Aug SU2 Human genetic variability (2) PM p. 92-96
- The scale of human genetic variation
6 1 Sept SU2 Human genetic variability (3) PM p. 190-199
- Pathogenic substitutions, insertions & deletions
7 6 Sept SU2 Human genetic variability (4) PM p. 124; 136-
- Pathogenic mutations by repetitive DNA 137; 201-209
8 8 Sept SU3 Consequences of human genetic variability (1) PM p. 212-220
- Chromosome abnormalities p. 220-228;
- Effects of pathogenic variants on the phenotype 236; 132

9
9 13 Sept SU3 Consequences of human genetic variability (2) PM p. 170, 180-
- Genomic imprinting 181
¾ E-assignment #1 (theory) made available on
ClickUP
10 15 Sept SU3 Consequences of human genetic variability (3) PM p. 237-239
- Modifier genes and environmental factors

11 20 Sept SU4 Identifying disease genes (1) WF p. 249-256

- Introduction
Due date: E-assignment #1 at midnight (00h00)
12 27 Sept SU4 Identifying disease genes (2) WF p. p256-265
- Linkage analysis
13 29 Sept SU4 Identifying disease genes (3) WF p. p259-273
- Complex diseases

1 OCT: SEMESTER TEST 1 (provisional date)

14 4 Oct SU4 Identifying disease genes & complex diseases( (4) WF p.273-285
- Association studies

UP RECESS: 6 - 8 October

15 11 Oct SU4 Identifying disease genes (5) WF p. p286-304

- Mapping complex disease by GWAS
16 13 Oct SU5 Treatment of genetic disorders and disease (1) WF p.309-317
- Introduction
17 18 Oct SU5 Treatment of genetic disorders and diseases (2) WF p. 336-353
- Gene therapy
¾ E-assignment #2 made available on ClickUP
18 20 Oct SU5 Treatment of genetic disorders and diseases (3) WF p. 354-369
- Gene therapy, animal models

19 25 Oct SU6 Cancer genetics and genomics (1) PM p. 373-397

- Fundamental characteristics
Due date: E-assignment #2 at midnight (00h00)
20 1 Nov SU6 Cancer genetics and genomics (2) PM p. 373-397
- Evolution of cancer

21 3 Nov SU6 Cancer genetics and genomics (3) PM p. 404-406

- Oncogenes & tumour suppressor genes
22 8 Nov SU7 Genetic testing (1) EH 431-435
- Overview
23 10 Nov SU7 Genetic testing (2) EH p. 435-440
- Testing for chromosome abnormalities

12 NOV SEMESTER TEST 2 (Provisional date)

10
24 15 Nov SU7 Genetic testing (3) EH p. 435-p445
- Testing for large-scale DNA changes
25 17 Nov SU7 Genetic testing (4) EH p. 446-457
- Testing for small-scale DNA changes
26 22 Nov SU7 Genetic testing (5) EH p. 458-463
- Prenatal testing
27 24 Nov SU7 Genetic testing (6) EH p. 467-477
- Reproductive genetic counselling
27 Nov Start of Examination period

1 DEC: EXAM (Preliminary date)

TUTORIALS
Online tutorials: Please keep your eye out for ClickUP announcements, which will give clear
instructions for what is expected for each tutorial. We expect you to work through the tutorial
problems as you would in a normal contact session, because these opportunities allow you to
prepare for test and exam-type questions. It is a compulsory aspect of this course. A few general
procedures that will apply to such tutorials are:

• Tutorial questions will be available on ClickUP at least a day before it is scheduled. You
should complete the tutorial before the official scheduled practical session each week. The
tutorial will then be discussed during an online Blackboard Collaborate session, at which
time you will have the opportunity to interact with the lecturers and ask questions related to
the work.

• You are required to upload a scan or cell phone picture of your completed questions to
ClickUP within 2 days of the official online session in order to meet the compulsory
attendance requirement for that tutorial. Please note that the answers you submit should
be hand-written and not typed. Selected questions will be marked at the discretion of the
lecturers. These marks will contribute to the Practical mark. A MEMO of the tutorial will be
posted online following your submissions, so that you can check your answers.

• We will not tolerate any duplicated submissions, and any students caught submitting
duplicated files/images will not receive an attendance record for that tutorial as they will be
guilty of plagiarism. You are welcome to meet by yourselves in groups and do the tutorial
"together", but you MUST then do the tutorial in your own book and upload evidence of
your own work separately.

• Following the tutorial submission deadline, and after issuing the memo, you may also be
asked to write a small (max 10 mark) online quiz based on the tutorial's content. You will
have two days to complete it, with multiple logins permitted to allow for internet
connectivity problems. These tests will count towards the practical mark of this module.

11
• The lecturer leading each tutorial will be available for the entire scheduled tutorial session
on Blackboard Collaborate or on the Discussion Forum, should there be questions about the
tutorial or the theory lectures. This will be the official consultation time for each lecturer,
but s/he may also schedule additional opportunities where students may submit questions
for the lecturer to address.

• Valid excuses for failing to complete a quiz, tutorial, assignment or assessment must be
submitted to Mrs Laubscher electronically within three days of the scheduled tutorial.

TUTORIAL TIMETABLE AND THEMES

PM: Dr Pontsho Moela WF: Dr Wilma Fick EH: Dr Engela Honey AL: Mrs Adrene Laubscher
Date Topic
TUT 1 (PM)
17 Aug GTS 368 course roadmap

TUT 2 (WF/AL)
24 Aug Conventional cytogenetic analyses of human chromosomes

DNA profiling
31 Aug TUT 3 (PM)
Introduction to Infographic group assignment & selection of ClickUP groups

7 Sept TUT 4 (PM) CaseIT software illustrated

TUT 5 (PM) CaseIT practical

14 Sept

TUT 6 (WF) Exploring human genome resources online

28 Sept

1 OCT: SEMESTER TEST 1 (provisional date)

Molecular analysis of a trinucleotide repeat disease

5 Oct TUT 7 (WF)
Tutorial test 1

UP RECESS: 6 - 8 October

12 Oct TUT 8 (WF) Linkage analysis

19 Oct TUT 9 (WF) Genome-wide association studies, CaseIT

26 Oct TUT 10 (PM) Cancer - melanoma and BRAF mutations, CaseIT

Gene therapy
2 Nov TUT 11 (WF)

9 Nov TUT 12 (EH, AL) Meet the people

12
12 NOV SEMESTER TEST 2 (Provisional date)

Genetic testing for chromosome abnormalities

16 Nov TUT 13 (EH)
Tutorial Test 2
23 Nov Revision session (all lecturers)

Please note that:

1) Smaller tutorial tests will be scheduled at hoc and announced timeously on ClickUP.

2) It is the responsibility of each student to purchase a hardcover A4 book dedicated to use

for the tutorials. Your completed hand-written answers should be submitted via ClickUP.
3) The study material from the tutorials will also be assessed in the semester tests and the
exam.
3.5 LEARNING PRESUMED TO BE IN PLACE
It is assumed that you are well-informed with regard to the fundamental principles of genetics
such as chromosomal basis of inheritance, single gene (Mendelian) inheritance, DNA structure,
replication, transcription, translation, basic principles of recombinant DNA technology, as well as
its applications. The concept of genetic variation and how it can be studied and exploited using
quantitative genetics, population genetics and molecular evolution. This course builds on this
prior knowledge and it is therefore to your own advantage to ensure that you are clued-up.

Critical cross-field outcomes:

• Identifying and solving problems by using critical and creative thinking
• Working effectively with others as a member of a team
• Organising and managing oneself and one’s activities responsibly and effectively.
• Collecting, analysing, organising and critically evaluating information
• Communicating effectively using visual and language skills in the modes of oral and
written persuasion
• Using science and technology responsibly, effectively and critically

13
3.6 CREDIT MAP AND NOTIONAL HOURS

This module carries a weighting of 18 credits, indicating that a student should spend an average
of 180 hours to master the required skills (including time spent in preparation of assignments as
well as preparing for tests and examinations). The scheduled contact time is approximately five
hours per week (2 lectures + 3hr practical), which means that another seven to eight hours per
week should be devoted to this module. This should include reviewing material prior to each
lecture as well as the material covered in the lectures and practical sessions as well as time spent
on assessment activities. Reviewing each study unit by completing the supplementary questions
and intensive study for the formal assessments. To determine whether you have mastered the
Table 1: A breakdown of the estimated learning time taken by the 'average' student to achieve the
specified learning outcomes of the module
Activity Time spent Frequency Total Total
(hours per (number of Minutes Hours
session) sessions)

Watching narrated 50 27 1350

PowerPoints 22,5
Live blackboard sessions 50 14 700
(recap difficult concepts,
work through example
questions, Q&A regarding
uploaded lectures, etc.) 11,66666667
Tutorials 180 13 2340 39
E-assignments 180 2 360 6
Tutorial tests 200 2 400 6,666666667
Own study time (Reading 185 14 2590
work/watching
videos/watching narrated
PPTs in preparation for
lectures and tuts) 43,16666667
Revision classes 180 1 180 3
Study for tests 745 2 1490 24,83333333
Test time 180 2 360 6
Study for exam 850 1 850 14,16666667
Exam 180 1 180 3
Total 10800 180
study unit answer the problems at the end of the chapters.

14
Your Faculty Student Advisor can advise you on goal-setting, adjustment to university life, time management, study
methods, stress management and career exploration. Book an individual consultation or attend a workshop. For other
support services see Section 5.

3.7 STUDY UNITS

STUDY UNIT 1: BASIC CONCEPTS IN HUMAN GENETICS

This study unit considers some of the most fundamental concepts in the field of human genetics.
In the first lecture, we will discuss the structural organisation of the human nuclear genome and
conventional methods by which the human karyotype can be studied on a cytogenetic level. The
second lecture, we will revise the basic inheritance patterns of single genes, previously discussed
in depth in GTS 161. The third lecture is dedicated to aspects of the human sex chromosomes
and X-chromosome inactivation.

Note: Factors that can complicate the interpretation of Mendelian inheritance patterns will be
discussed in more depth in Study Units 2 and 3.

LEARNING PRESUMED TO BE IN PLACE:

From GTS 161 and GTS 261: Structure of DNA, the cell cycle, mitosis and meiosis

From GTS 161 and GTS 351: Organisation and content of a eukaryotic genome, principles of
eukaryotic gene regulation, core DNA technologies.

Prescribed textbook: Chapters 1-3 relevant to fundamental concepts listed above.

STUDY MATERIAL
Textbook: Chpt 2 p. 34-36; Chpt 5 p. 117-131 (sections presented in lectures);

Chpt 6 p. 173-175; Chpt 7 p. 214-215; Chpt 11 p. 441-442

The following articles are not compulsory, but provide additional material for those interested:
• Wutz A. (2011) Gene silencing in X-chromosome inactivation: advances in understanding
facultative heterochromatin formation. Nature 12: 542-553.
• Brand, BA et al (2021) The Impact of X-Chromosome Inactivation on Phenotypic Expression of
X-Linked Neurodevelopmental Disorders Brain Sci. 11(7), 904

LEARNING OUTCOMES
After completing this study unit you should be able to do the following:

1. Describe the technique of preparing cells for conventional karyotyping and cytogenetic
analysis using the Giemsa banding technique.

2. Understand the way in which human chromosomes are distinguished based on

morphological features such as size, centromere position and banding patterns.

15
3. Have a working knowledge of the ISCN nomenclature and be able to interpret ISCN
abbreviations of abnormal karyotypes.

4. Discuss the principles of conventional fluorescence in situ hybridisation (FISH) and its
applications in human genetics.

Note: More advanced techniques will be discussed in Study Unit 7.

5. Have a working knowledge of the standard symbols used in compiling pedigrees.

6. Identify the correct inheritance pattern of single genes (Mendelian and mitochondrial)
from a given pedigree by applying your knowledge about the main features of each
inheritance type. Motivate your choice of inheritance pattern by providing supporting
evidence.

7. Explain why consanguinity increases the risk for autosomal recessive disorders.

8. Explain why X-linked recessive disorders are more prevalent in males. Which
circumstances may lead to an X-linked recessive disorder occurring in females and how
would their clinical symptoms compare with that of an affected male?

9. Explain why X-linked dominant disorders are usually more prevalent in females.

10. Explain how heteroplasmy influences the manifestation of mitochondrial diseases.

11. Compare the structural similarities and differences between the human X- and Y-
chromosomes.

12. Discuss the concept of X-chromosome inactivation by referring to the purpose and
timing of X-chromosome inactivation, genes that escape X-chromosome inactivation
and the molecular mechanism that leads to inactivation.

13. Explain the reason and consequences of non-random X-chromosome inactivation and
variable expression of X-linked genes in female heterozygotes

TERMINOLOGY

Karyotype, ideogram, metacentric, sub-metacentric, acrocentric, telomere, proximal, distal,

fluorescence in situ hybridisation.

Allele, homozygous, heterozygous, autosomal, dominant, recessive, carrier, X-linked, hemizygous,

monogenetic disorder, co-dominant, pedigree, proband, sib, kindred, consanguineous, compound
heterozygote, matrilineal Inheritance, heteroplasmy, , heteroplasmy.

Pseudo-autosomal region, dosage compensation, inactive X chromosome, clonal propagation, Barr

body, X-inactivation centre (Xic), X-inactivation specific transcript (XIST), facultative
heterochromatin, Polycomb group complex (PcG complex),

SELF-STUDY ACTIVITIES

16
1. Females affected with an X-linked dominant genetic disease usually show milder clinical
symptoms than males affected with the same disease and there is also a wider variability of
clinical manifestations between females. Explain why.

2. It is unusual to find a female affected with an X-linked recessive disease. Name instances that
can lead to this situation.

3. Don and his maternal grandfather both have hemophilia, an X-linked recessive disease. Don is
married to Dianne. Dianne and Don's mothers are sisters. Don and Dianne have 4 children;
their son Edward and daughter Enid are normal, but their daughters Elize and Emily are
hemophilics.

a. Construct a pedigree from the given information.

b. Given the fact that X-linked recessive disorders mostly affect males, explain why Elize
and Emily are hemophilics.

c. What is the probability that Enid would have a hemophilic son?

d. Explain in principle why the clinical manifestation of X-linked genetic diseases in

female carriers often varies from a normal phenotype to a very severe degree of the
genetic disease.

5. Explain how XXY males would be able to survive with a usually male-lethal X-chromosome
disorder (tip: skewed X-chromosome inactivation or somatic mosaicism).

STUDY UNIT 2: ORIGINS OF HUMAN GENETIC VARIABILITY

Learning presumed to be in place:

From GTS261 Basic principles of gene mutation and DNA repair; single-gene inheritance
From GTS161 Chromosome structure/number, cell cycle, mitosis and meiosis. From
Textbook: Chapter 1, sections 1.2, 1.3 & Figure 2.8

STUDY MATERIAL:
Textbook: p. 80-84; p. 92-96; p. 190-199; p. 124; p136-137; p201-209
Scientific article: Feero, W.G., et al., (2010). Genomic Medicine - An Updated Primer. New
England Journal of Medicine 362: 2001-2011.

KEY POINTS

v DNA sequence variants are common in the population, and range from single base
changes to large-scale DNA rearrangements.
v Mutations may occur spontaneously or can be induced by chemical or radiation
mutagens.

17
v The fidelity of the DNA sequence is maintained by a DNA repair system.
v Polymorphisms are sequence variants that occur commonly in the population.
v Sequence variants can be silent or may alter the quantity or quality of the gene product.
v Sequence variants can affect gene expression, the amino acid sequence of a protein, or
splicing.
v Advanced paternal age is associated with increased rate of mutation.
v Some disorders associated with the mutational mechanism of triplet repeat expansion
display the phenomenon of anticipation, where a disorder becomes more severe with
each passing generation.
v Genomic-level changes include copy number variants, inversions, and chromosomal
changes.
v Congenital anomalies occur in approximately 3% of pregnancies and are due to a wide
variety of both genetic and nongenetic causes. Some multiple congenital anomaly
syndromes are due to chromosomal abnormalities.
v abnormalities include deletions, duplications, inversions, rings, and translocations.

LEARNING OUTCOMES
After completion of this unit you should be able to:
1. Describe the types of DNA sequence variants.
2. Describe/explain the concept of genetic polymorphism.
3. Use the correct nomenclature to describe mutations/variants.
4. Explain the basis for paternal-age effect.
5. Explain how human chromosomes are distinguished based on morphological features
such as size, centromere position, satellites, etc.
6. Describe the indications for chromosomal analysis.
7. Describe triploidy, trisomy, reciprocal translocations, Robertsonian translocations,
paracentric inversions, and deletions.

SELF-STUDY ACTIVITIES
To determine whether you have mastered the study unit answer the problems at the end of the
chapters.

18
STUDY UNIT 3: CONSEQUENCES OF HUMAN GENETIC VARIABILITY

Learning presumed to be in place:

From GTS261 Basic principles of gene mutation and DNA repair; single-gene inheritance
From GTS161 Chromosome structure/number, cell cycle, mitosis and meiosis. From
Textbook: Chapter 1, sections 1.2, 1.3 & Figure 2.8

STUDY MATERIAL:
Textbook: p. 212-220; p. 220-228; p236; p132; p. 170, 180-181; p. 237-239
Scientific article: Feero, W.G., et al., (2010). Genomic Medicine - An Updated Primer. New
England Journal of Medicine 362: 2001-2011.

KEY POINTS

v Abnormalities of chromosome number or structure underlie many human developmental

disorders and cancer.
v The presence of one or more extra complete chromosome sets is referred to as
polyploidy, and usually is lethal.
v Aneuploidy is the presence of a non-integral number of the haploid set. A number of
aneuploidy syndromes have been characterized.
v Structural chromosomal
v Pseudo-dominant inheritance occurs when a homozygous individual and a heterozygous
individual mate. A recessive trait will thereby exhibit vertical transmission. It occurs
mostly with traits that are relatively common.
v Penetrance is defined as the existence of a phenotype in an individual with the at-risk
genotype. Non-penetrant individuals do not express the phenotype. There may be a
range of expressivity among individuals who are phenotypically affected.
v New mutations may account for sporadically affected individuals.
v Some individuals are mosaics for a mutation if the mutation arose post-zygotically. In
some cases, the mutation is confined to the germ-line.
v Uniparental disomy or deletion can underlie specific syndromes associated with
deficiency in imprinted genes.
v Genomic imprinting effects may lead to a disorder being manifest only if the gene was
inherited from the parent whose gene copy is expressed.

LEARNING OUTCOMES

After completion of this unit you should be able to:

1. Explain the origins of the main types of numerical and structural chromosome abnormalities.

19
2. Explain the role of imprinting in determining the phenotype of individuals with certain
chromosomal abnormalities.
3. Work out the main possible reproductive outcomes for carriers of translocations or
inversions.
4. Explain the implications of constitutional and mosaic chromosomal abnormalities.
5. Describe/discuss the nature of mutations and pre-mutations and how they contribute to
human variability and disease.
6. Describe /explain the pathogenesis of diseases of unstable repeat expansion.
7. Explain the phenomenon of anticipation.
8. Use specific examples of molecular pathology to describe how it defines phenotype.
9. Explain gain-of-function and loss-of-function mutations and how they relate to phenotype.
10. Explain the meaning of allelic and locus heterogeneity in human disease.
11. Give a general outline of the mechanisms by which disease-causing mutations produce
disease.
12. Explain/discuss how genomic imprinting effects may lead to a genetic disorder.

SELF-STUDY ACTIVITIES
To determine whether you have mastered the study unit answer the problems at the end of the
chapters.

STUDY UNIT 4: IDENTIFYING HUMAN DISEASE GENES & GENETIC SUSCEPTIBILITY TO

COMPLEX DISEASES

Learning presumed to be in place:

From GTS 251 / GTS 261 – Construction of genetic and physical genome maps, basic principles of
linkage mapping and GWAS studies. Principles of Next-Generation sequence technologies,
whole genome and exome sequencing.

STUDY MATERIAL:
Textbook: Chapter 8, p. 247 - 304
Scientific articles:
1. Pearson T.A. & Manolio T.A. (2008). How to interpret a Genome-Wide Association Study.
Journal of the American Medical Association 299(11):1335 - 1343.
2. Ng S.B., et al., (2010). Exome sequencing identifies the cause of a Mendelian disorder.
Nature Genetics 42:30-35
3. Gillssen, C., et al., (2011). Unlocking Mendelian disease using exome sequencing. Genome
Biology 12: 228 [doi:10.1186/gb-2011-12-9-228]

20
KEY POINTS
v Genetic linkage analysis provides a means for mapping the genome using the frequency
of recombination between loci as a measure of genetic distance.
v Linkage analysis in humans is accomplished by the calculation of lod scores.
v A variety of DNA sequence polymorphisms can be used as markers for linkage analysis.
v Positional cloning allows genes to be identified by first mapping the genes and then
cloning the DNA within the mapped region until the gene of interest has been found.
v Multifactorial traits are determined by a combination of genetic and non-genetic factors.
v Most common disorders include at least some genetic component. The identification of
these genes is a major goal of current research in human genetics.
v Genes that contribute to multifactorial disorders can be identified using single nucleotide
polymorphisms (SNPs) in association studies or transmission disequilibrium studies.
v Association studies identify haplotype blocks that harbour a disease susceptibility variant,
but identifying the causal variant is difficult.
v GWA studies have successfully identified many disease-associated SNP-markers, however
because almost all are of weak affect, they have limited use in predicting disease risk.

LEARNING OUTCOMES

After completion of this unit you should be able to:

1. Understand the principles of independent assortment and homologous recombination.
2. Explain how the frequency of recombination between loci can be used as a measure of
genetic distance.
3. Describe in outline how human disease genes can be tracked through a pedigree using
linked markers.
4. Discuss/explain how linkage is established and how LOD scores are calculated.
5. Understand the concepts of linkage equilibrium and linkage disequilibrium.
6. Describe how genes that contributes to complex traits (multifactorial disorders) can be
identified using SNPs in association studies.
7. Explain the difference between association and causation.
8. Discuss/explain the pitfalls of genome wide association studies (GWAS).
9. Compare and contrast Linkage and Association methods.
10. Discuss the advantages and disadvantages of whole exome sequencing for identification
of disease genes.
11. Appreciate the fact that incidental or secondary genetic findings can occur as a result of
whole exome sequencing.
12. Understand that health and disease occur as a consequence of complex interactions of
genetic and non-genetic (environmental) factors.

21
SELF-STUDY ACTIVITIES
To determine whether you have mastered the study unit answer the problems at the end of the
chapter.

STUDY UNIT 5: TREATMENT OF GENETIC DISORDERS AND GENETIC TREATMENT OF DISEASE

STUDY MATERIAL
Textbook: Chapter 9 p.309-317, p. 336-369
Scientific articles:
1. Collins M, Thrasher A (2015) Gene therapy: progress and predictions. Proc. R. Soc. B 282:
20143003. http://dx.doi.org/10.1098/rspb.2014.3003
2. Gonçalves, GA, de Melo Alves Paiva R (2017) Gene therapy: advances, challenges and
perspectives. Einstein (Sao Paulo) 15(3):369–375. doi: 10.1590/S1679-45082017RB4024

KEY POINTS
v A wide variety of approaches are being developed and applied to the treatment of genetic
disorders, including approaches that may lead to correction of a genetic mutation.
v The therapeutic approach needs to be tailored to the particular genetic disorder and, in
some cases, to the particular gene mutation.
v Gene therapy involves transferring genes, RNA, or oligonucleotides into the cells of a
patient so as to alter gene expression in some way that counteracts or alleviates disease.
The patient’s cells are often genetically modified in culture and then returned to the body.
v Gene therapy strategies often seek to compensate for underproduction of an important
gene product. Other strategies are designed to block the expression of a mutant gene that
makes a harmful gene product, or to induce alternative splicing so that a harmful
mutation does not get included in a mRNA, or to kill harmful cells, for example in cancer
gene therapy.
v Viral vectors are commonly used in gene therapy because they have good gene transfer
rates, but they sometimes provoke strong immune responses and also abnormal
activation of cellular genes such as proto-oncogenes
v In gene augmentation therapy, diseased cells that are genetically deficient for some
product are supplemented by transfecting a cloned gene to make the missing product
inside the cells.
v In vivo gene therapy involves the transfer of therapeutic constructs in situ within the
patient. Ex vivo gene therapy involves removing cells from a patient, genetically modifying
them in culture and returning the modified cells to the patient.
v Some therapies target RNA. In gene silencing, the expression of a positively harmful gene
(such as a gene with a gain-of-function mutation or one expressed by a pathogen) is
selectively repressed, usually by inhibiting the RNA. RNAs can sometimes also be induced
to undergo alterative splicing to counteract disease.

v Animal disease models are generated by genetically modifying the germ line to mimic a
human phenotype, but have limitations.

22
v Genome editing is a new approach to treat genetic diseases

LEARNING OUTCOMES
After completion of this unit you should be able to:
1. Discuss the conventional approaches to the treatment of genetic diseases and the general
status of gene-based therapies.
2. Explain the minimum requirements for gene therapy to treat a genetic disorder, and the
differences between somatic and germ-line gene therapy.
3. Compare the ex vivo and in vivo approaches of gene therapy, mentioning the advantages
and disadvantages of each.
4. Discuss the advantages and disadvantages of the different vectors used in gene therapy.
5. Discuss examples of gene therapy trials with specific emphasis on the reasons for the
failures of the therapy.
6. Write an essay on the risks, benefits, challenges and future directions of gene therapy.
7. Explain the concept of embryonic stem (ES) cells, cell reprogramming and induced
pluripotent cells (iPs). How are these applied in the field of human genetics?
8. Explain the principles of the two main strategies used to generate transgenic mice.
9. What are the advantages and limitations of different animal models?
10. Explain how RNA can be used to treat genetic diseases.
11. Explain the principles of genome editing and its applications in human genetics.

SELF-STUDY ACTIVITIES
1. There are two broad principles regarding the technological aim of somatic gene therapy: (a)
genetically modifying disease cells (without killing them), and (b) killing disease cells either
directly or indirectly. Explain what is involved in the two strategies.
2. Describe the characteristics of two viral vectors based on RNA genomes and two viral vectors
based on DNA genomes that are used in gene therapy.
3. Molecular therapeutic strategies sometimes target RNA instead of DNA. What is involved in
RNA interference therapy, and how useful has it been?

STUDY UNIT 6: CANCER GENETICS & GENOMICS

Learning presumed to be in place:

From GTS351 - Gene regulation and cancer

STUDY MATERIAL:
Textbook: Chapter 10, p373 – 407; Section 10.5, p418 - 424
Scientific article: Stadler Z.K., et al., (2014). Cancer genomics and inherited risk. Journal of Clinical
Oncology, doi: 10.1200/JCO.2013.49.7271

23
KEY POINTS
v Several lines of evidence support the idea that cancer is the result of genetic changes in
somatic cells.
v Two major types of genes that contribute to malignant change are tumor suppressor
genes and oncogenes.
v Tumor suppressor genes contribute to transformation to cancer when both alleles are
mutated. In some cases, one of the mutations is inherited, and the other acquired
somatically.
v Oncogenes are normal cellular genes that, when activated by mutation, convey abnormal
growth properties, contributing to malignancy.
v Oncogenes encode proteins that are involved in the signal transduction pathways
involved in stimulation of cell growth; tumor suppressor genes encode proteins involved
in regulation of growth.
v Progression toward malignancy is a multistep process due to the gradual accumulation
of genetic changes, including activation of oncogenes and loss of function of tumor
suppressor genes.
v Knowledge of the molecular basis of cancer is being used to develop new methods of
diagnosis and treatment.
v Genetic predisposition to cancer is recognized by a pattern of familial transmission, as
well as characteristics such as early age of onset and multifocal disease
v A number of cancer predisposition syndromes have been identified, and some of these
are subject to genetic testing.
v A positive genetic test result for cancer predisposition can be helpful in planning a
program of surveillance or institution of medical or surgical approaches to risk reduction.
It can also provide a basis for genetic counselling of family members.
v Like all predisposition tests, cancer genetic test results must be interpreted with caution,
since not all individuals will develop cancer, and there are both risks and benefits to being
tested.

LEARNING OUTCOMES

After completion of this unit you should be able to:

1. Explain the basic biology of cancer.
2. List the essential capabilities of malignant tumours and describe the types of somatic
genetic changes that lead to their development.
3. Describe the properties / function(s) of proto-oncogenes and tumour suppressor genes
and list some examples.
4. Describe the mechanisms involved in the conversion of proto-oncogenes to oncogenes.
5. Using retinoblastoma, explain/discuss the different mechanisms for the loss of the
wildtype allele of a tumour suppressor gene.
6. Explain the Knudson theory.

24
7. Describe the types of genomic instability found in cancer cells.
8. Using appropriate examples explain/discuss the multi-step evolution of cancer.
9. Discuss the syndromes associated with increased susceptibility for specific malignancies
and the genes involved.
10. Distinguish between the genes/processes involved in inherited susceptibility to cancer
and sporadic forms of cancer.
11. Describe the role of genetics/genomics in diagnosis, treatment and prevention of cancer.
12. Have an appreciation for possible unintended consequences of cancer genomic testing.

SELF-STUDY ACTIVITIES
To determine whether you have mastered the study unit answer the problems at the end of the
chapters.

25
STUDY UNIT 7: GENETIC TESTING FROM GENES TO GENOMES

Learning presumed to be in place: From textbook, Chapter 3

STUDY MATERIAL:
Textbook: Chapter 11, p431 – 474; Box 11.1; Box 11.2 and Box 11.3
Scientific articles:
1. Korf B.R. & Rheim H.L. (2013). New approaches to molecular diagnosis. New England Journal
of Medicine 309(14):1511-1521.
2. General descriptions of methods for scanning a gene for mutations can be found in Strachan
T and Read AP. Human Molecular Genetics, 2nd edition. Garland, New York - freely available
as searchable text on the NCBI Bookshelf :
http://www.ncbi.nlm.nih.gov/entrez/queryfcgi?db=Books
3. Wapner, R. J. et al., (2012). Chromosomal microarray versus karyotyping for prenatal
diagnosis. New England Journal of Medicine 367: 2175–2184
4. De Jong, A., et al., (2011). Advances in prenatal screening: the ethical dimension. Nature
Reviews Genetics 12: 657–663

KEY POINTS
v Identification of the gene for a disorder permits diagnostic testing by direct mutation
analysis.
v Some genetic disorders are associated with a wide range of allelic heterogeneity.
v Genetic testing may reveal variants of unknown significance that require special care in
interpretation.
v Molecular genetic tests are often first developed in research laboratories, but clinical
testing requires transfer of the test to a certified clinical laboratory.
v Genetic linkage analysis can be used to track a genetic trait through a family if the
responsible gene is not known or mutations cannot be easily identified.
v Genetic tests raise a number of potential ethical issues that should be considered in
deciding to initiate testing.
v New-borns can be screened for an increasing variety of conditions on the principle that
early detection can lead to therapy that prevents severe, long-term medical problems.
Technological advances are quickly expanding the scope of new-born screening.
v Children diagnosed with inborn errors of metabolism require lifelong care. An unexpected
consequence of PKU is a risk of congenital anomalies in the child of an affected woman
due to phenylalanine toxicity if the mother is not maintained on strict dietary control
during pregnancy.
v There is a wide variety of pathophysiological mechanisms that underlie inborn errors of
metabolism. These include defects in enzymes and coenzymes, with physiological
consequences of product deficiency and/or substrate accumulation.

26
v A variety of approaches to the treatment of inborn errors of metabolism are in use or in
development, including dietary management, coenzyme supplementation, removal of
toxic metabolites, enzyme replacement, and gene therapy.
v Carrier screening involves testing of individuals for heterozygosity for genes that would
produce significant disorders in the homozygous state. Couples found to be at risk if both
partners are carriers can be offered counselling regarding their options to deal with the
risk.
v An individual may be at increased risk of being a carrier for a particular genetic trait on
the basis of ancestry. Many screening programs are targeted toward particular groups
known to be at risk.
v Couples found to be at risk have many options, including prenatal diagnosis, adoption,
use of an egg or sperm donor, or planning for the medical needs of an affected child.
v Congenital anomalies occur in approximately 3% of pregnancies and are due to a wide
variety of both genetic and nongenetic causes.
v Some multiple congenital anomaly syndromes are due to chromosomal abnormalities.
v Analysis of chromosomes can be performed by collecting dividing cells in culture, swelling
the cells in hypotonic saline, fixing the chromosomes onto slides, and staining them with
a variety of special stains.
v The technique of fluorescence in situ hybridization (FISH) can be used to detect small
deletions or identify chromosomes involved in complex rearrangements.
v Genomic microarrays permit the detection of deletions or duplications at high resolution.
v Molecular cytogenetic analysis, including fuorescence in situ hybridization (FISH) and
array comparative genomic hybridization, are now being used to provide molecular
characterization of submicro-scopic chromosomal anomalies. This form of cytogenetic
testing is now recommended as the first tier of testing in individuals with intellectual
disability or autism spectrum disorders.
v Prenatal diagnosis by amniocentesis is commonly offered to women, especially those
over 35 years of age due to an increased risk of trisomy, especially trisomy 21.
Biochemical screening is being used to screen pregnancies for risk of trisomy.
v Traditionally prenatal diagnosis has used invasive procedures, in non-invasive prenatal
testing (NIPT), samples of freely circulating DNA recovered from maternal plasma are
analysed
v In pre-implantation diagnosis genetic testing occurs on embryos produced by in vitro
fertilization (assisted reproduction)
v In prenatal genetic counselling information is provided and support is given in a
nondirective manner.
v Genetic counsellors present all options in a neutral manner and support the couple
whatever decision they make.

27
v The decision to implement a carrier-screening program requires careful assessment of
risks and benefits and provision of counselling, testing, and management resources.
Carrier test results require careful interpretation and counselling of the couple.
v Genomic approaches are beginning to be applied to carrier screening, making it possible
to significantly expand the scope of conditions for which screening is provided.
v Genome-wide association studies have revealed single-nucleotide polymorphisms (SNPs)
in which specific alleles are associated with risk of various common disorders.
v Genotyping of individuals for specific SNPs can be used to estimate risk of disease, though
the tests are not diagnostic.
v Direct-to-consumer genome-wide genetic tests are available and provide information on
risk of disease, carrier status for some recessive disorders, some pharmacogenetic traits,
and information about some other common nonmedical phenotypes.
v Genetic tests for disease risk should be evaluated in terms of analytical validity, clinical
validity, and clinical utility, as is the case for other genetic tests.
v A distinction can be made between predictive tests, which identify whether an individual
has inherited a gene mutation that may eventually lead to a genetic disorder, and
predispositional tests, in which an individual may be found to be at increased or
decreased risk of a multifactorial disorder.

LEARNING OUTCOMES
After completion of this unit you should be able to:
1. Know of the common molecular diagnostic techniques and how they are applied to
diagnose genetic disease.
2. Understand and be able to describe the circumstances in which a DNA test involves
scanning a gene for mutations or checking for a specific change.

3. Have an appreciation of the possibilities as well as the limitations of genetic testing.

4. Describe /explain the criteria used to determine whether a nucleotide change is
pathogenic.
5. Have an understanding of the basic elements involved in direct and indirect testing.
6. Evaluate genetic tests for disease risk in terms of analytical validity, clinical validity and
clinical utility.
7. Discuss the principles of fluorescence in situ hybridisation (FISH) and comparative
hybridisation.
8. Understand and be able to discuss the potential advantages, limitations and
disadvantages of pre-symptomatic testing for genetic disease.
9. Estimate recurrence risks for Mendelian and certain multifactorial conditions in affected
families.
10. Have an understanding of the goals of screening programmes for genetic diseases in
newborn infants, pregnant women and other adults, and the ethical issues involved.

28
11. Know what the difference is between screening and diagnosis.
12. Distinguish between predisposition tests, where risk assessment for a multifactorial
disorder is through SNP analysis, and predictive tests, which determine whether a person
has inherited a gene mutation that may eventually lead to a genetic disorder.
13. Discuss prenatal screening for chromosomal abnormalities.
14. Compare and contrast chorionic villus sampling and amniocentesis.
15. Understand and be able to discuss non-invasive prenatal genetic testing.
16. Know the purpose as well as the elements of genetic counselling.
17. Understand and be able to describe the parameters commonly used to define the
performance of a screening programme.
18. Know the technical, social and ethical requirements that a screening programme should
fulfil.
19. Be able to discuss the advantages and disadvantages of screening programmes to
individuals and to society.
20. Have an appreciation for the ethical, legal and social issues that may be raised by genetic
and genomic tests.
21. Have a consideration of the ethical questions concerning reproductive choice, autonomy
rights of future children and equity of access with regards to prenatal testing/screening.

SELF-STUDY ACTIVITIES
To determine whether you have mastered the study unit answer the problems at the end of the
chapters.

4. ASSESSMENT
4.1 ASSESSMENT PLAN

Two semester tests will be written in this module. The dates and venues will be posted on
ClickUP. The memorandum will be available on ClickUP following completion of assessment. Any
papers requiring corrections or a remark need to be handed in or emailed to Mrs Adrene
Laubscher (Room 7-36 Agriculture Building).

Preliminary dates
Semester test 1: 1 October 2021
Semester test 2: 12 November 2021
Sick tests: 22 November 2021, provisional (All work covered for Semester tests 1 & 2)

Final dates, times and venues for tests will be available from the “timetables” link on the UP
portal and on the GTS368 ClickUP page.

29
Students who miss a semester test should send a valid medical certificate to Mrs Adrene
Laubscher ([email protected]) within 3 working days of the scheduled date of the
semester test. Failing to do so will disqualify him/her from writing the sick test. NOTE: There will
only be one sick test, regardless of which test was missed, that is written at the end of the
semester and that covers all the work. Students who miss both semester tests cannot substitute
this with a single sick test, and will be given exam entry refusal. PLEASE note that the same
regulations with regards to accepted sick notes apply for the entire module. Students will not be
admitted to the examinations without a semester test mark!

4.2 ASSESSMENT POLICY

CALCULATION OF MARKS
THEORY MARK: = Average of Semester test marks
PRACTICAL MARK: = Tutorials tests (average) and assignments (weighted) in a 80:20 ratio
SEMESTER MARK: = Theory mark, E-assignments and Practical mark in a 70:10:20 ratio
FINAL MARK (Scenario 1 ) = Semester mark and Examination mark in a 50:50 ratio (if written
exam)
FINAL MARK (Scenario 2 ) = Semester mark and Examination mark in a 60:40 ratio (if online exam)

Examination policy
According to the regulations of the Faculty of Natural and Agricultural Sciences, students with a
semester mark below 40% are refused entrance into the exam. The final pass mark for the
course is 50%. Sub-minimum regulations apply in that an exam mark of at least 40% must be
obtained to pass the module.
A final mark of at least 40% is required to qualify for a supplementary exam as scheduled by the
Faculty. There will be a perusal opportunity to view your exam paper prior to the supplementary
examination. A supplementary exam comprises a new paper different from the original exam.
Subject to other faculty regulations, a student must obtain a final mark of at least 50% in order
to pass a supplementary examination. The semester or year mark is not taken into account and
the supplementary mark is the final mark. A maximum of 50% can be obtained for the
supplementary exam.
All requests for a special exam will be handled by Student Administration. Please hand all sick
notes, etc. to Administration within three (3) working days of the missed exam. Students
wanting to write the special exam will not be allowed to enter the examination venue if the
Department has not been notified by Administration that they have been admitted writing a
special exam. The exam will be scheduled at the convenience of the lecturers.

Sick notes (Medical certificate)

Valid original sick notes are accepted if issued by a medical doctor registered at the Health
Professions Council of South Africa (HPCSA). The only other type of sick note that is accepted are

30
those issued by an Advanced Practice Nurse (a registered nurse with a postgraduate
qualification) as determined by the South African Nursing Council who has a BHCF practice
number, provided that the diagnosis falls only within their specific field of specialisation.

Affidavits
An affidavit will only be accepted if supported by substantiating documentation, e.g. case report
or criminal charge with case number obtained from a police station, valid medical certificate for
injuries, a death certificate for a funeral, etc. Please note that submission of fraudulent sick
notes and affidavits is a criminal offense, which will lead to disciplinary action and may result in
dismissal.

Approach followed in assessment

Students will be tested on their ability to interpret/apply/analyse and evaluate the knowledge
gained from each study unit, rather than merely conveying the facts. Tests and exams will
therefore generally be in the form of paragraph/essay type questions (up to 20 marks) and
interpretation of data. Knowledge, comprehension, synthesis and the ability to interpret will be
assessed. Students will be expected to integrate different sections of the work and to indicate
similarities or differences.

4.3 PLAGIARISM
Plagiarism is a serious form of academic misconduct. It involves both appropriating someone
else’s work and passing it off as one’s own work afterwards. Thus, you commit plagiarism when
you present someone else's written or creative work (words, images, ideas, opinions,
discoveries, artwork, music, recordings, computer-generated work, etc.) as your own. Only hand
in your own original work. Indicate precisely and accurately when you have used information
provided by someone else. Referencing must be done in accordance with a recognised system.
Indicate whether you have downloaded information from the Internet. For more details, visit the
library’s website:
http://www.library.up.ac.za/plagiarism/index.htm.

5. SUPPORT SERVICES
Please download a QR code reader on your cell phone. To download a QR code reader open your
mobile app store (App Store, Google Play or Windows Marketplace) and search for QR code
readers.

5.1 SAFETY IN THE EVENING AND EMERGENCIES

• For any safety or emergency related matters, e.g. if you need a security officer to
accompany you from your residence to campus, phone the Operational Management
Centre (details at the back of your student card).

31
• The 24-hour, multi-disciplinary UP Crisis Line offers professional and confidential support
to victims of crime in times of trauma. For assistance and immediate action, phone the
UP Crisis Line on: 0800 00 64 28.
• Hatfield residence students: From 18:00 till 06:00 security officers are available to escort
you (on foot) to and from your residence or campus anywhere east of the Hatfield
Campus through to the Hillcrest Campus.

5.2 E-LEARNING SUPPORT

• Report a problem you experience to the Student Help Desk on your campus.
• Visit the open labs in the Informatorium Building or IT labs on your campus to report
problems at the offices of the Student Help Desk.
• Approach the assistants at the help desks—campus specific (for example: adjacent to the
Student Computer Laboratories in IT Building, NW2, CBT or Aldoel Building IT labs, etc).
• Call 012 420 3837.
• Email [email protected]

32
5.3 OTHER SUPPORT SERVICES
• Think carefully before
dropping modules (after the
closing date for amendments
or cancellation of modules).
FLY@UP: www.up.ac.za/fly@up
• Make responsible choices
The Finish
with your time and work
Line is Yours email: [email protected]
consistently.
• Aim for a good semester
mark. Don’t rely on
the examination to pass.
Academic support for students
with learning disabilities:
• Assistive technological
services
https://www.up.ac.za/disabilityu
• Facilitation of test
nit
and examination
Disability accommodations
012 420 2064
Unit • Test and exam concession
email: [email protected]
applications
• Accessible study venues and a
computer lab
• Referrals for recommended
textbooks in electronic
format

Student
Provides counselling and 012 420 2333
Counselling
therapeutic support to students
Unit

Student
Promotes and assists students 012 420 5233
Health
with health and wellness 012 420 3423
Services

Provides support for UP students [email protected]

The Careers
and graduates as they prepare 012 420 2315
Office
for their careers

33
24-hour Operational 012 420-2310
Department of Management Centre 012 420-2760
Security
Services 24-hour Operational Manager 083 654 0476
Crisis Line 0800 006 428
Enquiries concerning studies,
Department of
accommodation, food, funds, 012 420 2371/4001 Hatfield
Student social activities and personal Roosmaryn Building,
Affairs problems campus

Centre for
Sexualities, Identifies and provides training of
012 420 4391
AIDS and student peer counsellors
Gender

Fees and http://www.up.ac.za/enquiry

012 420 3111
funding www.up.ac.za/fees-and-funding

012 420 3051

IT Helpdesk For student IT related queries [email protected]

34