Medical

Genetics
Dr. Md. Abedur Rahman
 Published by
Dr. Farzana Iqbal

First published………. January, 2005.

©MD. ABEDUR RAMMAN

AII rights reserved. No part of this book may be
reproduced or transmitted in any form or
by any means without the written permission of the
author.

Price: Taka 45/=-only.

For all kinds of correspondence

ABEDUR RAHMAN
Phone: 0189050041

2
 Dedicated to
My Uncle

Dr. Md. Nazrul Islam

MBBS, M. Phil (DU), MS (Glasgow),
MHPED (Australia)

Prof. of anatomy
Bangladesh government
and
Ex Vice president, BMA.
(Now working in Dept. of
Anatomy
University Sans Malaysia)

3
 for his broad minded personality that makes
him acceptable to all

Acknowledgements
I want to acknowledge following persons for their help
and inspiration during writing this book.
1. My respected teachers,
• Professor Md Ruhul Amin,
Head of the Department Of Physiology,
Dhaka Medical College and
Scientific Secretary, BMA.
• Dr Nazmul Huq
Associate Professor of Physiology, NICVD
• Dr Abida Ahmed
Associate Professor of Physiology, DMC,
as they have tolerated my shortcomings (during
writing this book) to obey their commands.
2. Roopa, my wife,
because she has tolerated my absence to my
family during writing this book.
3. Dr Md Shariful Islam Bhuiya, Dept. of eye, DMCH
Dr Ranzu, Dept. of eye, DMCH
Dr Rana, AR, MU- green, DMCH
Dr Golam Mostofa, Dept. of pediatrics, DMCH
Dr Reza, Dept. of medicine, SSMCH.
Dr Kayes, Dept. of medicine, SSMCH.
Dr Sarwar, NICVD.
Dr Mithu, Dept. of neurosurgery, SSMCH.

4
for their help and inspiration during writing this
book.

Author’s sayings

1.
2. Introduction to
genetics

This is a very simplified

presentation of
genetics. It outlined the
subject genetics in a
‘very easy to
understand’ way.

5
Let me know if the book becomes helpful to you. Best
wishes for all.

Abedur Rahman

Contents

1. Introduction To Genetics 7
2. Cellular And Molecular Basis Of 12
Inheritance
3. Terminology 30
4. Mutation 35
5. Pattern Of Genetic Disorder 39
6. Developmental Genetics 54
7. Diagnosis Of Genetic Diseases 59
8. Clinical Genetics 68
9. Genetic Counselling 83
Glossary 85

References

6
 1. Muller Robert F, Young Ian D: Emery’s Elements
Of Medical Genetics, 11th Edition
2. Datta A K: Essentials of Medical Genetics.
3. Davidson’s principle and practice of medicine
4. Inderbir Singh: Textbook Of Human Histology
5. Cotran Ramzi S, Kumar Vinoy, Collins Tucker:
Pathologic Basis Of Diseases
6. Guyton A C: Textbook of Medical Physiology.
7. Ghai O P: A Textbook of Pediatrics.
8. Khan M R, Ekhlasur Rahman: A Textbook of
Pediatrics.
9. Dawn C S: A Textbook of obstetrics.
10. Ganong William F: Review of Medical Physiology.

PROPER MANAGEMENT
OF HIGH BLOOD
PRESSURE
Most mild and moderate degree of high blood
pressure can be controlled by non drug management,
although a number of patients need medication. Non
drug management includes life style modification,
restriction of some food etc.
You may find a proper guideline for recent advances
on non drug control of High Blood Pressure in the
following book. The book also speaks about different
medicines (with recent advances) of high blood

7
pressure, that is, how high blood pressure medicines
can be used properly in different patients.

HIGH BLOOD
PRESSURE: AN
UPDATE
(Coming soon)

Written by:
Dr Md Abedur Rahman

Persons with high blood pressure

and those who want to prevent
high blood pressure can further
consult here:

DR MD ABEDUR RAHMAN
MBBS (DMC), M Phil (Thesis part- on blood pressure and lipid
profile)
Post graduate training on Cardiology
Chamber: Shaheen Diagnostic Centre
85/A, Hosni Dalan Road, Chankharpul, Dhaka
Phone: 0189050041, e-mail: [email protected]

8
 3.
4. Introduction to
genetics

Genetics is the science that deals with the

transmission of characters from parents to offspring.

Mendel’s law
In his breeding experiments Mendel studied
contrasting characters in the garden pea, using for
each experiment varieties which differed in only one
characteristic. For example, he noted that when
strains which were bred for a feature such as tallness
were crossed with plants bred to be short, all the
offspring in the first filial or FI generation were tall. If
plants in this Fl generation were interbred, then this
led to both tall and short plants in a ratio of three to
one (Fig. below). Those characteristics which were
manifest in the F1 hybrids were referred to as
dominant, whereas those which reappeared in the F2
generation were described as being recessive. On re-
analysis it has been suggested that Mendel's results
were 'too good to be true', in that the segregation
ratios he derived were suspiciously closer to the value
of 3:1 than the laws of statistics would predict. One
possible explanation is that he may have published
only those results which best agreed with his
preconceive single gene hypothesis. Whatever the
truth of the matter, events have shown that Mendel's
interpretation of his results was entirely correct.
Mendel's proposal was that the plant characteristics
being studied were each controlled by a pair of
factors, one of which was inherited from each parent.

9
A Danish botanist Johannsen subsequently coined the
term ‘gene’ for these hereditary factors. The pure
bred plants, with two identical genes, used in the
initial cross would now be referred to, as
homozygous. The hybrid F1 plants, each of which has
one gene for tallness and one for shortness, would be
referred to as heterozygous. The genes responsible
for these contrasting characteristics are referred to as
allelomorphs or alleles for short.

First filial cross

Pure bred short
X
tt

F 1
Tt Tt Tt Tt

Tall
Tall Tall Tall

Hybrid Hybrid
Tall X Tall
Tt Tt

TT Tt tT tt
Tall Tall Tall Short
F2

Fig. : An illustration of one of Mendel's breeding

experiments and how he correctly interpreted the
results.

On the basis of Mendel's plant experiments, three

main principles were established. These are known as
the laws of uniformity, segregation and independent
assortment.
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THE LAW OF UNIFORMITY
The law of uniformity refers to the fact that when two
homozygotes with different alleles are crossed, all the
offspring in the Fl generation are identical and
heterozygous. In other words the characteristics do
not blend, as had been believed previously, and can
reappear in later generations.

THE LAW OF SEGREGATION

The law of segregation refers to the observation that
each individual possesses two genes for a particular
characteristic, only one of which can be transmitted
at any one time. Rare exceptions to this rule can
occur when two allelic genes fail to separate because
of chromosome non-disjunction at the first meiotic
division.

THE LAW OF INDEPENDENT ASSORTMENT

The law of independent assortment refers to the fact
that members of different gene pairs segregate to
offspring independently of one another. In reality,
this is not always true as genes which are close
together on the same chromosome tend to be
inherited together, i.e., they are linked.

Chromosomes
Chromosomes are elongated thread-like structures
which become visible during cell division in the
nucleus.
Chromosomes consist of two major parts
1. The DNA and
2. Protein (histone)

Gene
• Gene is a portion of DNA (composed of segments of
DNA) within which genetic information is stored.
• These genes are responsible for transmission of a
particular character from generation to generation.
• Genes are arranged within the chromosomes like
beads on a string.
(M.R. Khan & Ekhlasur Rahman, Essence of Pediatrics)
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From gene to characters
DNA (gene) determines the type of messenger
ribonucleic acid (mRNA) that is synthesized by a cell;
mRNA is responsible for the type of protein
manufactured by the cell. The proteins that are
manufactured may be structural proteins or enzymes.
Together these determine how the cell looks and
what it does. The characteristics of individual cells
collectively make up the characteristics of the whole
organism.
Only 3 percent of DNA in the human genome
symbolizes genes. About 97 percent of the DNA has
no clear cut function and is flippantly termed as "Junk
DNA". Many copies of the latter type of DNA are
scattered at random over the chromosomes
intermingled with genes. These are called repetitive
sequences. These are useful for fingerprinting of the
human genome. There are about 50,000 to 1 lakh
genes in the human beings. Roughly 20 percent of
these are specific genes which regulate the
production of structural or functional proteins. About
80 percent genes are housekeeping genes responsible
for basic cell functioning. Highly related genes are
clustered in a particular region of chromosomes.

Flow of genetic information

Replication Transcription Translation

DNA DNA
mRNA
protein
(Gene) tRNA
rRNA

The Human Genome Project

The Human Genome project was launched in year
1989. The aim of the project was to determine the
complete nucleotide sequence of the human genome
(about 3 billion base pairs) by year 2005. By
sequencing, the structure and function of a gene and
its mutations leading to various disorders can be
studied. But the scientists have almost finished the

12
job earlier. In 26th June, 2000, scientist declared the
rough but almost complete arrangement of human
genes. It is the human genome sequence. In another
word, it is the blue print of men. Francis Collins and
Craig Venter are the two pioneers in this discovery.
Table: Genetic discoveries which have led to the award of the Nobel Prize
for Medicine and/or Physiology.1962-1999.
Year Prize-winners Discovery

1962 Francis Crick The molecular structure of DNA

James Watson
Maurice Wilkins

1965 Francois Jacob Genetic regulation

Jacques Monod
Andre Lwoff
1966 Peyton Rous Oncogenic viruses

1968 Robert Holley Deciphering of the genetic code

Gobind Khorana
Marshall Nirenberg
1975 David Baltimore Interaction between tumour viruses and
Renato Dulbecco nuclear DNA
Howard Temin
1978 Werner Arber Restriction endonucleases
Daniel Nathans
Hamilton Smith

1980 Baruj Benacerraf Genetic control of immunological response

jean Dausset
George Snell

1983 Barbara McClintock Mobile genes (transposons)

1985 Michael Brown Cell receptors in familial

Joseph Goldstein hypercholesterolaernia

1987 Tonegawa Susumu Genetic aspects of antibodies

1989 Michael Bishop Study of oncogenes

Harold Varmus

1993 Richard Roberts 'Split genes'

Phillip Sharp

1995 Edward Lewis Homeotic and other developmental genes

Christiane Nusslein-
Volhard
Eric Wieschaus

1997 Stanley Prusiner Prions

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1999 Gunter Blobel Protein transport signaling

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