Sex-linked And Mitochondrial Inheritance

Question 1

X chromosome characteristics

Answer 1

. 160 Mb base pairs
. 416 number of sequences genes 
. 37 known phenotypic descriptions 
. Metacentric centromere location 
. Meiotic recombination: over entire lengths for XX in females

Question 2

Y chromosome characteristics

Answer 2

. 70 Mb base pairs 
. 47 sequences genes 
. 0 known phenotypic descriptions 
. Acrocentric centromere location 
. Meiotic recombination of short arms of X and Y in males

Question 3

Lyonization

Answer 3

. X-inactivation
. Explains how X-linked gene products are equalized in males and females (equalization = dosage compensation)
. Process is random so maternally and paternally-derived X chromosomes will each be inactivated in about half of embryo’s cells
. Due to x-inactivation all normal females have 2 distinct populations of cells: one w/ an active paternally derived X chromosome and the other w/ an active maternally-derived X chromosome

Question 4

Unfavorite lyonization

Answer 4

. Inactivation of normal gene so mutated gene is active

. Results can be the expression of disease phenotypes in female carrier of an x-linked disorder

Question 5

X-linked dominant inheritance

Answer 5

. Twice as many females as males
. Affected females usually heterozygous, have 50% chance of passing disease allele to children
. No father to son transmission, all daughter of affected fathers inherit disease gene
. Vertical transmission w/ no skipped generations
. Occurrence/recurrence depends upon affected parent’s gender

Question 6

X-linked dominant disorders

Answer 6

. Fragile X syndrome
. Hypophosphatemic rickets: kidneys impaired in ability to reabsorbed phosphate resulting in ossification w. Bending of bones
. Incontinentia pigmenti type I: abnormal skin pigmentation, conical /missing teeth, ocular and neurons issues, only found in females bc hemiazygos males do not survive to term

Question 7

Fragile x syndrome

Answer 7

. Most common cause of inherited intellectual disability in males
. Large ears, long faces, hyper mobile joints
. Macroorchidism (inc. testicular volume) in post pubertal males
. Intellectual disability tends to be milder and more variable in females than males
. Has 80% penetrance in males and 30% penetrance in females (lower penetrance from x-inactivation)

Question 8

Fragile x syndrome disease gene

Answer 8

. Cloned and named FMR1
. FMR1 normally encodes FMRP protein
. Individuals normally produce FMRP, those who do not produce it then generate FMR1 gene
. Mutation: inc. CGG repeat unit in 5’ untranslated region
. Males w/ intermediate number of repeats do not show phenotype but pass it to offspring and in their female offspring bc there is an expansion of repeats when passed to daughters so their children will have disease
. Expansion does not occur in male offspring

Question 9

Y-linked inheritance

Answer 9

. 50-60 unique genes
. SRY gene: if deleted XY individuals will have range of testicular defects resulting in ambiguous gonads or female ones, little/no sperm production
. Deletions in azoospermia Factor (AZF) A, B, or C cause issues w/ proteins needed for sperm development
. Strictly father to son only

Question 10

Retinitis pigmentosa

Answer 10

. Inherited disease of eye where cells of retina produce defective proteins
. Progressive loss of sight starting w/ dec. night vision, loss of peripheral side vision, then blindness
. Autosomal dominant or X-linked recessive
. May be caused by RPY gene (Y-linked)

Question 11

X-linked recessive inheritance

Answer 11

. Horizontal transmission w/ skipped generations
. Mostly males affected
. Occurance/recurrence is 25% overall (50% boys, 0% girls
. No father to son transmission
. Diseases: red-green colorblindness, G6PD deficiency, hemophilia A/B, muscular dystrophy, Lesch-Nyhan

Question 12

Red-green colorblindness mating options and results

Answer 12

. X-linked recessive
. Normal male w/ carrier female: 1/2 sons normal, 1/2 colorblind, all daughters normal but carriers
. Colorblind male w/ normal female: all sons normal, daughter carries
. Colorblind male w/ carrier female: half sons and daughter colorblind, 1/2 daughter carriers, 1/2 sons normal
. Normal male and colorblind female: all sons colorblind, all daughters carriers

Question 13

Mitochondrial inheritance

Answer 13

. Mitochondrial DNA inherited exclusively from mother

. Mode of inherited considered pseudo-sex-linked

Question 14

Mitochondrial diseases

Answer 14

. Leber hereditary optic neuropathy: rapid loss in vision in central visual field as result of optic n. Death in 3rd decade of life, most severe in males
. Kearns-Sayre disease: muscle weakness, cerebellar damage, heart failure
. Pearson syndrome: infantile pancreatic insufficiency, pancytopenia and lactic acidosis