Lecture 6 - Role of Sex Inheritance Flashcards
X-linked Recessive Inheritance
- males much more affect (hemizygotes)
- male’s daughter only gets if mother hetereozygote
- affect male cannot pass to their son
- Horizontal Transmission (Criss Cross)
X-linked Recessive in Hetereozygote Females
If gene product:
1) Soluble Protein:
- like hemophilia
- she will average (less clotting protien)
2) localized to specific cell type:
- mosaic
Hemophilia
-mutation/inversion –> lack of Coag factor
Pathomechanism of Hemophilia
- 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
Duchenne Muscular Dystrophy Patomechanism
-large deletion of Dystrophin gene –> frame shit –> no dystrophin
(needed to connect F-actin to Sarcomere)
Symptoms of Duchenne Muscular Dystrophy
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))
Becker Muscular Dystrophy
small deletion of dystrophin –> INFRAME mutation
Similarity of Becker and Duchenne
-allelic Heterogenity
Peroxismal Disease
- neurological disease -> due to defect in Perioxismal Enzyme
- ALD (x-linked neonatal illness) -> Adrenoleuko dystrophy
Symptoms of Peroxisomal Disease
- progressive Demylination + Adreno insufficiency
- Gait problem
- Progressive demenetia
- Downhil to Veg state –> lethal w/i 16 months
Orthonine Transcarbaylase Defeciency (OTC)
- mut in OTC (gene = Xp21)
- usually converts Carbamyl-P –> Orthonine
- lead to accumulation of NH4
Treatment of OTC
- low protein diet
- med that are scavenge N
Androgen Insensitivity Syndrome (AIS)
T-receptor Mutation
-> genotypic XY males will have all female Genitalia
Kallman syndrome
Failure of GnRH-secreting cells to migrate along olfac axons to hypothalamus
–>Secondary Hypogonadism –> no secondary sexual character
Absence of Olfac Bulbs = Anosomia
Favism
-defect in G6PD (normally makes NADPH + protects RBC -> lead to Hemolysis induced by flava beans)
triggers of Favism
- Flava beans
- moth balls
- aspirin
- henna
All X-linked Recessive Diseases
- kallman syndrome
- Androgen Insensitivity syndrome
- Flavism
- Hemophilia
- OTC Def
- Duchenne + Beckers
X-linked Dominant Inheritance
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
Fragile X
- 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
Pathomech with Fragile X
-expansion of CGG in FMR1 gene -> when repeats >200 –> CpG islands hypermethy –> siliences Gene
Rett Syndrome in Males and in Females
- Males: Lethal
- Females: Prog Neurogen (hand-wringing)
Pathomechanism of Rett Syndrome
- 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
Sex-Influenced Traits
Sex-Influenced traits are inherited Autosomally
-> but have higher penetrance in 1 sex compared to other
Example of Sex-Influenced Traits
BALDNESS
- allele is dominant in males/recessive in females
- 5a-reductase: Test -> DHT
Pathomechanism of Baldness
- immune cells react to follice by yielding DHT
- DHT undermines absorpbtion of Biral Nutrients in Dermal Papilla
Sex-limited Traits
- autosomal gene whose expression is limited to 1 sex (req specific hormone for expression)
- either Male or Female
Pathomechanism of Precocious Puberty
- only expressed in males
- either mother/father can transmit this (reciprocal cross)
pmech: LHR mutation causes T to be produced w/o mutation
Cytoplasmic Inheritance
-cytoplasmic genes inherited from one parent only
Hetereoplasmy
- more than one mtDNA variant present
* proportion of mutant mtDNA that make it into ovum –> determine penetrance + severity
Y-linked Inheritance characteristic
- affects males only
- all sons of affected male will be affected
- vertical pedigree
SRY
Sex Determining Region on Y-> resp for male characteristics
-Y chromosome SRY –> test determing factor –> BIpotential primordia
Azospermia
Y-linked trait
- not inheritable
- men with AZF deletion
- when intracytomplasmic sperm injection –> transmit deletion
Genetic Maternal Effect
-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)
Example of Genetic Maternal Effect
-coiling of snail shells
