Lol Application of Genetic Principles

Autosomal Dominant Inheritance

I
IT I
Dmale
0 female
11 diseased
I 1 I pregnant
I II agender undetermined
DTO left born first

vertical pattern inheritance

from one generation to next generation
both females males are attested
variable expression same disease but different effect

eg BRCA1 can be ovarian 1 breast cancer

have the gene 4 has
inurn let e 1 complete penetrance the disease
have 1 e gene but does not have the disease
7
WHY
G da t existence of modifier gene variant
atteet severity penetrance

eg F GFR 2 variants in BRC 2 mutation carriers

Other examples AD conditions mostcoloncancergenes

AV
BRCA1 13kt Lynchsyndrome are AD exceptMUTYHgene
Inherited breast 1 colon cancer
APKD ie ADPKD
NFL neurofibromatosis 2 FH
achondroplasia VFamilial Hypercholesterolemia
tuberous sclerosis HCM v Apertsyndrome
Hypertrophic cardiomyopathy
Autosomal Recessive Inheritance
father mother

carrier parents Aa Aa
1
offspring AA Aa Aa a a

diseased
normal carrier
50 5
25

Pedigree chart
D O 17 0

btbto
o b lo do it
if it's AR child is atteited assume parents
are carriers

only those with homozygous gene gets the disease

WM pound heterozygous on same gene 2 different
mutations

double heterozygous fault in one gene on anothergene

46
normally 23 pairs of chromosomes
trisomy Down's syndrome 3 chromosome M total 47

triploidy 69 chromosomes
 y

usually horizontal not vertical

attested individuals in one sibship
both males females are equally attested
there may be consanguinity in the
murmur family
property of being from the same kinship as another person

Examples of Ak conditions
cystic fibrosis vsickle cell disease

phenylketonuria PKU

spinal muscular atrophy SMA

1 El
congenital adrenal hyperplasia
congenital adrenal hypoplasia X linked 3

Autosomal Dominant vs Autosomal Recessive

X linked Recessive Inheritance
F
TO
l l
7.0
I
III 11 0 II II I 1.0

it it
O
it
II
itD
I I I DTO IT
0 I DTI
features
knight's move pattern not horizontal vertical
jumps around
no male to male
mostly 1 only males are affected

occasional manifesting carriers

due to skewed X inactivation
lyonization one of the X chromosome is inactivated
in the embryo

Expected proportions of offspring of a female heterozygote

father mother carrier
parents XY X Xd Xiadiseased
1
offspring XY Xdy XX XX d
H H H a
normal diseased normal carrier
boy boy girl girl
 son 50 being affected
daughter 50 being carrier

Expected proportions of offspring of a mare heterozygote

attested father mother

parents XDY XX

offsprings XY Xy Xd X X DX
normal boys carrier girls

son 0 affected
daughter i 100 carrier

Examples of X linked recessive

spinal muscular atrophy
Haemophilia A
Red color blindness
green

linked dominant inheritance

ATO
I I I I
ATO a ITO l
F ITO II I Gatto
I E f E b b a
 Examples
uit D resistant rickets usually but sometimes AD
incontinent'ta pigment's has male lethality
Rett syndrome atteets children male lethality usually

X linked recessive vs dominant

Mendelian Inheritance
Atypical
Genetic Anticipation
As you go down the pedigree in successive generations 3

v increasing severity
earlier age of onset

mutation in
gene is presented as repeat sequence
when passing it on more repeat sequence
gets worse

examples
Huntington Disease CHP
 fragile X syndrome
myotonia dystrophy

ITO
aoia.ua

1 I
asrepfaa.is
I
I 1
II arepeats

ageof onset
family with HD number a repeats

pseudo dominant Inheritance

unusual y if an AR condition but has a
very high
carrier frequency 1 consanguinity
it appears like AD

TO DTI
in
EH ETO a
ab O b I

eg Gilbert syndrome
carrier in 50
frequency
intermittent jaundice
dlt unconjugated hyperbillmblnemia
 Mitochondrial Inheritance
much smaller genome several chromosome copies in
each mitochondria heteroplasm
circular
only 16 6 Kb reach certainlevel of heteroplasmy
manifest disease
37 genes
no introns

inherited only from the mother maternal inheritance

all children inherit it from the mother but to
extents
variable
syndromes often affect muscle brain eyes

eg Leigh's disease
the affected mitochondrial DNA
MT ATP 6 genes
ATP
synthase

Three person baby

step 1
mother'segg
intonemaintahr
ruffed

Donor egg
destroyed
healthy
mitochondria
Summary
Autosomal Dominant
vertical pattern

equalfrequency severity in male female

variable expressibllHy

Autosomal resistant
horizontal pattern
equalfrequency severity in male female
carriers usually unattested

x linked recessive
NO male to male transmission

females unattested or
mildly affected
DH skewed X inactivation

Atypical inheritance Inweasing severity decreasingage

Genetic anticipation of onset in successive generations
mutation might be in more than one
Gonadal mosaicism egg sperm in the parentsgonads
pseudo dominant
InheritancerwYY.ITas aofvery highcarrierfreq
an attunedmother
all offspring
mitochondrial in her HMU will beaffected none of offspring
of an attectedfather