X-linked inheritance XD, XR

Question 1

Heterogametic

Answer 1

Y from father,X from mother XY

Question 2

Pseudoautosomal region

Answer 2

region of homology b/w X and Y chromosomes exists at the tip of their short arms.
In males, prophase I, homologous pairing b/w X and Y chromosomes occurs at pseudoautosomal segments

Question 3

Holandric Inheritance

Answer 3

Y-linked genes are transmitted from father to son.

Question 4

Genes on sex chromosomes

Answer 4

X chromosomesd~500 genes, Y~fewer genes known, SRY close to pseudoautosomal region, H-Y histocompatibility antigen-gene for hairy ear and genes involved in spermatogenesis

Question 5

Males are always . . . .

Answer 5

HEMIZYGOUS. never homozygous or heterozygous

Question 6

Dosage compensation

Answer 6

females with XX and males with XY, EXPRESS X-LINKED GENES ESSENTIALLY AT THE SAME LEVEL

Question 7

Lyon’s Hypothesis

Answer 7

explains disparity b/w gene dosage and the level of expression of X-linked genes: Only 1 X is transcriptionally active, inactive X is a Barr Body/Sex chromatin. Inactivation occurs early in embryonic life and random and permanent. . . thereafter the same X is inactivated in all daughter cells

Question 8

X Chromosome inactivation

Answer 8

Achieved by methylation of CpG dinucleotides in the promoter regions. X inactivation is incomplete: 3 classes of genes escape inactivation
Genes at and outside psuedoautosomal region. E.g. steroid sulfates-> plasma level high in females (deficiency->Icthyosis:fish-like scaley skin

Question 9

X Non-random inactivation

Answer 9

when karyotype involves a structurally abn X:deletions, duplications, and isochromosome, the ABN X will be inactivated.
Cells prefer to keep the autosomal gene active

Question 10

Manifesting heterozygotes

Answer 10

mutated allele is present on active X on all or most cells

Question 11

Asymptomatic heterozygotes

Answer 11

mutant allele preferentially on inactive X in most or all cells
EX:color blindess, hemophilia A and B, DMD,Wiskott-aldrich syndrome (immunodeficiency)

Question 12

X-linked recessive inheritance

Answer 12

phenotype more frequent in males, man transmits gene to ALL daughters, NOT transmitted from father to son. Can be transmitted through female carriers for generations.
May be CONSANGUINITY.
Sig proportion are new mutations (DMD)

Question 13

X-linked Recessive and males.

Answer 13

No male-to-male transmission! males are more affected b/c they are homozygous.

Question 14

X-R: Mutation? Characteristics? Duchenne’s muscular dystrophy (DMD)

Answer 14

Dystrophin gene, frame-shift deletions. Onset 3-5 yrs, wheelchair bound by 12 yrs.
Dystrophin protein maintains sarcolemmal stability.
Musculare degeneration, pseudohypertrophy, death in 20s due to respiratory insufficiency

Question 15

X-D: Mutation? Characteristics? Fragile X syndrome

Answer 15

CGG at 5’ UT region.
Defect in FMR-1 transcription-hypermethylation and silencing.
Mental retardation, oversized jaws and ears, enlarged testes, temper tantrums.

Question 16

X-R: Mutation? Characteristics? Hemophilia A

Answer 16

Mutation in Factor VIII
Uncontrolled bleeding.
Both factor 8 and 9 are required for activation of factor X in intrinsic coagulation path.
Males predominantly affected

Question 17

X-R: Mutation? Characteristics? Hemophilia B

Answer 17

Mutation in Factor IX

Uncontrolled bleeding

Question 18

X-R: Hemophiliia A and B

Answer 18

Sxs depend on degree of deficiency.
NEONATAL BLEEDING-> intracranial hemorrhage, severe hematoma, prolonged bleeding from cord or umbilical area.
SOFT-TUSSUE HEMORRHAGE-trauma related
HEMARTHROSIS-bleeding into joints
HEMATOMA formation after mild trauma, bruise easily
PROLONGED PARTIAL THROMBOPLASTIN TIME(PPT-intrinsic)
Normal PT-extrinsic pathway

Question 19

X-linked Dominant inheritance

Answer 19

regularly expressed in heterozygotes.
Affected males(with normal mates) have:
~all daughters affected, No sons affected.
Hemizygous males are generally more severely affected.
No male-to-male transmission.
both male and female offspring have 50% chance of inheriting the phenotype

Question 20

X-linked Dominant inheritance: IF THE FATHER IS AFFECTED

Answer 20

if the father affected, the mutant allele always goes to the daughter.
All the sons of affected fathers will be normal.

Question 21

X-linked Dominant inheritance: IF THE MOTHER IS AFFECTED

Answer 21

If mutant allele is in mother, there is an equal chance for the sons +daughters to get it.

Question 22

X-linked Dom Disorders: Resistant Rickets

Answer 22

Rickets despite adequate Vit. D.
Characterized by LOW PLASMA AND HIGH URINARY PHOSPHATE LEVELS.
due to IMPAIRED ABILITY OF KIDNEY TUBULES TO REABSORB FILTERED PHOSPHATE->X-LINKED HYPOPHOSPHATEMIC RICKETS.
females usually less severe skeletal changes than males.

Question 23

X-linked Dom Disorders: Ornithine Transcarbamoylase (OTC) deficiency

Answer 23

UREA CYCLE ENZYME->absent->LETHAL NEONATAL.
HYPERAMMONIEMIA in affected males.
heterozygous females exhibit wide variation on OTC levels and clinical severity.
INCOMPLETELY DOMINANT-X-LINKED DISORDER

Question 24

X-linked Dom Disorders: Lethal in males: Rett Syndrome

Answer 24

RETT SYNDROME-mental disorder that appears to be PRENATAL LETHAL IN HEMIZYGOUS MALES, AND PRECLUDE REPRODUCTION IN AFFECTED FEMALES.
occurs exclusively in females, who are the only cases in the families. (males die early) Considered to be new mutations.

Question 25

X-linked Dom Disorders: Lethal in males: Incontinentia Pigmenti 2

Answer 25

lethal in hemizygous males:microcephaly, small/absent teeth, loss of hair, swirling skin rash,erythema, vesicles, mental retardation.
Female heterozygotes->totally nonrandom X-inactivation->X chromes carrying IP2 mutant are inactive.

Question 26

Genetic Heterogeneity

Answer 26

Includes a number of phenotypes that are similar, but different genotypes at different loci.