Mendelian Inheritance II Flashcards
(54 cards)
what is hemizygosity?
having only one member of a chromosome pair or segment, rather than 2 (males are homozygous for the X chromosome)
describe X-linked recessive d/o (5)
- single mutant allele for males and two mutant alleles for females needed to cause disease
- never passed father to son
- incidence of trait higher in males
- males more severely effected
- affected man will transmit to all of his daughters
when will females be affected by x-linked recessive d/o?
1- homozygous female- 45,X (turner syndrome)
2- translocation of X and autosome with preferential inactivation of the normal x (only express mutant X)
3- skewed x inactivation- mutant X expressed more
4- females are homozygous for the mutation (two affected Xs)
discuss male-male inheritance of X-linked d/o?
father will not pass on to son bc he gives son Y, not X
why is the phenotype for x linked recessive more severe for males than females?
due to hemizygosity of the X in males, the mutant allele is fully expressed
what is X inactivation?
only one of the X chromosome’s genes are expressed in each cell so that males an females express the same dosage of X-linked genes
describe x-linked dominant d/o
lethal in the homozygous state (no affected males)
what are the recurrence risks for an affected mother with an X-linked dominant d/o?
33% unaffected daughter
33% affected daughter
33% unaffected son
affected son will to survive
what are examples of X linked dominant d/o?
goltz syndrome- usually de novo
incontinentia pigmenti- inherited or de novo
rhett syndrome
what is a trinucleotide repeat d/o?
described by the expansion (within affected gene) of a segment of DNA that contains a 3 nt repeat
what is “expansion”?
increase in the number of repeats that is passed to subsequent generations, eventually leading to expression of the d/o
what d/o was trinucleotide repeat first discovered?
fragile X syndrome
what is repeat size in trinucleotide repeat d/o?
of repeats, allows for range of phenotype from mild to severe
what is anticipation in trinucleotide repeat d/o?
the occurrence of a disease at an earlier age of onset or with increasing severity in successive generations, basis for anticipation is expansion of the repeats
what are 4 common trinucleotide repeat d/o?
Huntington’s disease
fragile X
Myotonic dystrophy
Friedrich ataxia
what are “long expansions” in trinucleotide repeat d/o?
repeat usually more than 10x normal size, present outside the coding region, CCG/CGG or CTG, assoc with fragile sites in some cases
examples of long expansion trinucleotide repeat d/o
fragile X, FXTAS, FRAXE, myotonic dystrophy, spinocerebellar ataxia type 8
what is the age of onset of myotonic dystrophy type 1?
20-40
what are the sx of myotonic dystrophy type 1?
muscular weakness, wasting, cardiac arrhythmia, cataracts, male balding/infertility
what is the inheritance pattern for myotonic dystrophy type 1?
autosomal dominant
when is anticipation a factor with myotonic dystrophy type 1??
when it is inherited from the mother
10% risk of congenital myotonic dystrophy type 1
what gene is affected in myotonic dystrophy type 1?
19q13, myotonin protein kinase
what/where is the repeat in myotonic dystrophy type 1?
CTG, 3’-UTR
what are the normal/asymptomatic/affected/congenital repeat ranges for myotonic dystrophy type 1?
normal- 5-35
asymptomatic- 35-49 *risk for expansion
affected- over 50
congenital- large # (1000s)
