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Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
INTRODUCTION TO MEDICAL
GENETICS
Atif Amin Baig
Medical lecturer,
Faculty of Medicine and Health Sciences,
Universiti Sultan Zainal Abidin
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
What is Genetics?
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Impo rtanc e o f g e ne tic s
Genetics
G×E
interaction
Environment
Health
2005
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1991
Number of journal records
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
ISI Web of Science topic search for "genetic AND disease"
8000
7000
6000
5000
4000
3000
2000
1000
0
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Branc he s o f g e ne tic s

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
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Medical Genetics.
Plant genetics.
Population genetics.
Cytogenetics.
Molecular genetics.
Oncogenetics.
Nutrogenetics.
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Ge no me S ize
Species
Size in bps
Amoeba dubia
670,000,000,000
Homo sapiens
3,400,000,000
Drosophila melanogaster
Mycoplasma genitalium
Human immunodeficiency virus
180,000,000
580,000
9,750
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Locus – lo c a tio n o f a gene/marker o n th e c h ro m o s o m e .
Allele – one variant form of a gene/marker at a particularlocus
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Ge no me and g e ne s

Gene: basic unit of genetic information. Genes determine the inh e rite d c h a ra c te rs .

Genome: th e c o lle c tio n o f g e ne tic info rm a tio n.

Chromosomes :s to ra g e units o f genes.

DNA : is
a nuc le ic a c id th a t c o nta ins th e g e ne tic DNA
ins truc tio ns s p e c ifying th e b io lo g ic a l d e ve lo p m e nt o f a ll c e llula r fo rm s o f life Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
The p he no ty p e o f an o rg anis m d e no te s its e xte rnal ap p e aranc e (s iz e , c o lo r, intelligence,
etc.).
Clas s ic al g e ne tic s s ho w e d that g e ne s c o ntro l the transmission of phenotype from one generation to the
next.
Bio c he m is try showed that within one generation, prote ins had a de te rm ining e ffe ct on phenotype.
Improved phenotype in high yield
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Bio te c hno lo g y
Ge ne tic
Eng ine e ring
Modified phenotype can be
helpful for mankind in different forms
Phenotype can be achieved by
changing the genetic code
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Me nde l Inhe ritanc e
Australian monk who formulated
fundamental law of heredity in early 1860s.
The o rie s o f inhe ritanc e s
Gregor Mendel
(1822-1884)
Re s huffling o f g e ne s fro m g e ne ratio n to g e ne ratio ns
Vienna
He studied mathematics at University of
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
One trait inhe ritanc e

Mendel performed cross-breeding experiments between
true breeding plants (homozyous).

Choose varieties that differed in only one trait
(monohybrid).

Performed crosses:
Parental generation =P
First generation offspring =F1 (1st filial)
Second generation offspring =F2 (2nd filial)



Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Law o f s e g re g atio n


Each individual has two factors
for each trait.
The factors separate when
gametes form.

A gamete contains only one of
two factors.

Fertilization =new individual
with 2 factors for each trait.
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Ge no type Vs Phe no type
Ge no type
Refers to the alleles an individual receives
Ge no typic fre que nc y
Frequency of specific allelic recombination
RR : Rr : rr
1 :2 : 1
Phe no type
Refers to the physical appearance of the individual
Phe no typic fre que nc y
Round : Oval
3
: 1
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Mo de rn g e ne tic s and Law o f
s e g re g atio n

E.g. if you have one allele for brown eyes
(B) and one for blue eyes (b), somatic
cells have Bb and each gamete will carry
one of B or b chosen randomly
Sperm
B
Eggs
b
B BB Bb
b
Bb bb
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Me nde l’s law o f do minanc e

If your two alleles are different (he te roz ygous , e.g. Bb), the trait
associated with only one of these will be visible (dominant) while
the other will be hidden (recessive). E.g. B is dominant, b is
recessive.
Sperm
B
Eggs
b
B BB Bb
b
Bb bb
Genotypic frequency: BB : Bb : bb
1 : 2 :1
Phenotypic frequency:
Brown : Blue
3 : 1
o minant alle le : The allele which is always visible phenotypically or through its action
e c e s s ive alle le : The allele which is only visible phenotypically if no dominant allele is prese
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Me nde l’s law o f inde pe nde nt
as s o rtme nt

Knowledge of which allele has been inherited at one
locus gives no information on the allele has been
inherited at the other locus
S /s
Y/y
SY
Sy
sY
sy
25%
25%
25%
25%
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Me nde l’s law o f inde pe nde nt
as s o rtme nt
Gametophytes
(gameteproducing
cells)
S
Y
s
y
monohybrid cross
dihybrid cross (2n)
Segregation
Gametes
S
Y
s
y
A
b
a
B
Recombinants
Alle le s fo r d iffe re nt traits are dis tribute d to s e x c e lls (& o ffs pring ) inde pe nde ntly o f o ne an
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Dihybrid c ro s s
Traits : S e e d s hape & S e e d c o lo r
 Alle le s : R ro und
r wrinkle d
Y ye llo w
y g re e n


RrYy x RrYy
RY Ry rY ry
RY Ry rY ry
All possible gamete combinations
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
RY
RY
Ry
rY
ry
Ry
rY
ry
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Dihybrid Cro s s
RY
Ry
RY RRYY RRYy
Ry RRYy
rY RrYY
ry
RRyy
RrYy
rY
RrYY
RrYy
rrYY
ry
RrYy
Rryy
rrYy
Round/Yellow:
Round/green:
9
3
wrinkled/Yellow: 3
wrinkled/green: 1
RrYy
Rryy
rrYy
rryy
9:3:3:1 phenotypic
ratio
22
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
LAW
PARENT CROSS
OFFSPRING
DOMINANCE
TT x tt
tall x short
100% Tt
tall
Tt x Tt
tall x tall
75% tall
25% short
RrGg x RrGg
round & green x
round & green
9/16 round seeds & green pods
3/16 round seeds & yellow pods
3/16 wrinkled seeds & green pods
1/16 wrinkled seeds & yellow pods
SEGREGATION
INDEPENDENT
ASSORTMENT
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Inc o mple te Do minanc e
F1 hybrids have an appearance somewhat
in be twe e n the phe no type s of the two
parental varieties.
 Example : s napdrag o ns (flo we r)
 re d (RR) x white (rr)
r
r



RR = re d flo we rR
rr = white flo we r
R
24
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Inc o mple te Do minanc e
r
r
R Rr
Rr
produces the
F1 generation
R Rr
Rr
All Rr = pink
(heterozygous pink)
25
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Co do minanc e
Two alle le s are e xpre s s e d (multiple
alle le s ) in he te ro zyg o us individuals .
 Example : blo o d type





1.
2.
3.
4.
type
type
type
type
A
B
AB
O
=
=
=
=
IAIA o r IAi
IB IB o r IBi
IAIB
ii
26
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
S e x-linke d Traits
Example: Eye color in fruit flies
S e x Chro mo s o me s
fruit fly
e ye c o lo r
XX c hro mo s o me - fe male
Xy c hro mo s o me - male
27
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
S e x-linke d Traits


Example : Eye c o lo r in fruit flie s
(re d-e ye d male ) x (white -e ye d fe male )
XRY






x
XrXr
Re me mbe r: the Y c hro mo s o me in male s do e s
no t c arry traits .
RR = re d e ye d
Xr
Xr
Rr = re d e ye d
rr = white e ye d
XR
XY = male
XX = fe male
Y
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
S e x-linke d Traits
Xr
XR X X
R
Y
Xr Y
Xr
r
X X
R
Xr Y
r
50% red eyed
female
50% white eyed
male
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
Mitochondrial inheritance



This type of inheritance applies to genes in mitochondrial DNA.
Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children. E.g. Leber's hereditary optic neuropathy (LHON)
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
S o me c o mmo n g e ne tic
dis o rde rs

Cystic fibrosis – disease affecting the mucus lining of
the lungs, leading to breathing problems and other
difficulties.
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
S o me c o mmo n g e ne tic
dis o rde rs
Huntington disease

Huntington's chorea is an
inherited
disorder
characterized by abnormal
body
movements
called
chorea, and loss of memory.
There also is evidence that
doctors as far back as the
Middle Ages knew of this
devastating disease. The
incidence is 5 to 8 per
100,000. It takes its name
from the New York physician
George Huntington who first
described it precisely in 1872.
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
S o me c o mmo n g e ne tic
dis o rde rs


Hemophilia
illne s s that impair the body's ability to control bleeding.
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011
S o me c o mmo n g e ne tic
dis o rde rs

Fragile X syndrome - is a
genetic condition that causes
a range of developmental
problems including learning
disabilities
and
mental
retardation. Usually males are
more severely affected by this
disorder than females. In
addition
to
learning
difficulties, affected males
tend to be restless, fidgety,
and
inattentive.
Affected
males
also
have
characteristic
physical
features that become more
apparent with age.
Nature Precedings : doi:10.1038/npre.2011.6596.1 : Posted 12 Nov 2011