Lecture 6 - Role of Sex Inheritance

Question 1

X-linked Recessive Inheritance

Answer 1

• males much more affect (hemizygotes)
• male’s daughter only gets if mother hetereozygote
• affect male cannot pass to their son
• Horizontal Transmission (Criss Cross)

Question 2

X-linked Recessive in Hetereozygote Females

Answer 2

If gene product:

1) Soluble Protein:
- like hemophilia
- she will average (less clotting protien)

2) localized to specific cell type:
- mosaic

Question 3

Hemophilia

Answer 3

-mutation/inversion –> lack of Coag factor

Question 4

Pathomechanism of Hemophilia

Answer 4

• intron 22 contains 2 small genes (F8A + F8B)
• intra-chromosomal crossing over during meiosis –> inversion of these pieces –> F8 gene falls apart

-occurs mostly in paternal gene

Question 5

Duchenne Muscular Dystrophy Patomechanism

Answer 5

-large deletion of Dystrophin gene –> frame shit –> no dystrophin

(needed to connect F-actin to Sarcomere)

Question 6

Symptoms of Duchenne Muscular Dystrophy

Answer 6

GOWER SIGN: difficulty to stand at age of 2-3
-wheelchair by 10 -> death by 20
-most men do not reach reproductive age
(disease still here = spont mut of dystrophin (maternal germline))

Question 7

Becker Muscular Dystrophy

Answer 7

small deletion of dystrophin –> INFRAME mutation

Question 8

Similarity of Becker and Duchenne

Answer 8

-allelic Heterogenity

Question 9

Peroxismal Disease

Answer 9

• neurological disease -> due to defect in Perioxismal Enzyme
• ALD (x-linked neonatal illness) -> Adrenoleuko dystrophy

Question 10

Symptoms of Peroxisomal Disease

Answer 10

• progressive Demylination + Adreno insufficiency
• Gait problem
• Progressive demenetia
• Downhil to Veg state –> lethal w/i 16 months

Question 11

Orthonine Transcarbaylase Defeciency (OTC)

Answer 11

• mut in OTC (gene = Xp21)
• usually converts Carbamyl-P –> Orthonine
• lead to accumulation of NH4

Question 12

Treatment of OTC

Answer 12

• low protein diet

- med that are scavenge N

Question 13

Androgen Insensitivity Syndrome (AIS)

Answer 13

T-receptor Mutation

-> genotypic XY males will have all female Genitalia

Question 14

Kallman syndrome

Answer 14

Failure of GnRH-secreting cells to migrate along olfac axons to hypothalamus

–>Secondary Hypogonadism –> no secondary sexual character

Absence of Olfac Bulbs = Anosomia

Question 15

Favism

Answer 15

-defect in G6PD (normally makes NADPH + protects RBC -> lead to Hemolysis induced by flava beans)

Question 16

triggers of Favism

Answer 16

• Flava beans
• moth balls
• aspirin
• henna

Question 17

All X-linked Recessive Diseases

Answer 17

• kallman syndrome
• Androgen Insensitivity syndrome
• Flavism
• Hemophilia
• OTC Def
• Duchenne + Beckers

Question 18

X-linked Dominant Inheritance

Answer 18

Affected Father:

• > All daughters affected
• > Sons not

Affected Mum:
-> give to 1/2 sons and 1/2 of daughter

• Ratio of diseased Female = 2x
• Vertical Transmission

Question 19

Fragile X

Answer 19

• single gene defect with Variable Penetrance
• 20% Male: Asymptomatic
• 50% Hetereozygotes Females: Retardation (x-inact)
• clinical severity increase with each gen due to progressive expansion of triplet repeat

Question 20

Pathomech with Fragile X

Answer 20

-expansion of CGG in FMR1 gene -> when repeats >200 –> CpG islands hypermethy –> siliences Gene

Question 21

Rett Syndrome in Males and in Females

Answer 21

• Males: Lethal

- Females: Prog Neurogen (hand-wringing)

Question 22

Pathomechanism of Rett Syndrome

Answer 22

• Insertion/deletion/substitution in MECP2
• MECP found alot in Brain (respon for synapse reg + gene expr/alt splicing)
• Germline mut in Mother’s OVum –> resp for Daughter getting it

Question 23

Sex-Influenced Traits

Answer 23

Sex-Influenced traits are inherited Autosomally

-> but have higher penetrance in 1 sex compared to other

Question 24

Example of Sex-Influenced Traits

Answer 24

BALDNESS

• allele is dominant in males/recessive in females
• 5a-reductase: Test -> DHT

Question 25

Pathomechanism of Baldness

Answer 25

• immune cells react to follice by yielding DHT

- DHT undermines absorpbtion of Biral Nutrients in Dermal Papilla

Question 26

Sex-limited Traits

Answer 26

• autosomal gene whose expression is limited to 1 sex (req specific hormone for expression)
• either Male or Female

Question 27

Pathomechanism of Precocious Puberty

Answer 27

• only expressed in males
• either mother/father can transmit this (reciprocal cross)

pmech: LHR mutation causes T to be produced w/o mutation

Question 28

Cytoplasmic Inheritance

Answer 28

-cytoplasmic genes inherited from one parent only

Question 29

Hetereoplasmy

Answer 29

• more than one mtDNA variant present

* proportion of mutant mtDNA that make it into ovum –> determine penetrance + severity

Question 30

Y-linked Inheritance characteristic

Answer 30

• affects males only
• all sons of affected male will be affected
• vertical pedigree

Question 31

SRY

Answer 31

Sex Determining Region on Y-> resp for male characteristics

-Y chromosome SRY –> test determing factor –> BIpotential primordia

Question 32

Azospermia

Answer 32

Y-linked trait

• not inheritable
• men with AZF deletion
• when intracytomplasmic sperm injection –> transmit deletion

Question 33

Genetic Maternal Effect

Answer 33

-maternal genotype affects offspring phenotype

(egg is much larger than sperm –> mum provides majority of cytoplasm –> cytoplasm fill with maternal gene products which affects developing embryo)

Question 34

Example of Genetic Maternal Effect

Answer 34

-coiling of snail shells