Inheritance

Question 1

Recessive mutation

Answer 1

Two copies of mutant gene (homozygous)

Question 2

Dominant mutation. Could be due to (4)

Answer 2

Only 1 copy of mutated allele results in phenotype.

(1) haploinsufficiency (copy number loss)
(2) Dominant negative (gene product of mutation interferes with proper functioning of gene
(3) Gain of fn for protein
(4) Random loss of allele

Question 3

Compound heterozygous

Answer 3

2 recessive alleles, but each allele is mutated in different locations

Question 4

Locus (genetic) heterogeneity

Answer 4

Mutations at two or more loci result in similar phenotype

Question 5

Allelic heterogeneity

Answer 5

Different mutations in the same gene may result in same disease

Question 6

Phenotypic heterogeneity

Answer 6

Different mutations in same gene may result in different phenotypes

Question 7

Autosomal dominant

Answer 7

Vertical transmission; males and females equal risk and transmit equally; males pass to males; parents often affected; complicated by penetrance (mutation may not result in phenotype), variable expressivity (multiple phenotypes), new mutation, pleiotropy (affects multiple things)

Question 8

Mosaicism

Answer 8

Presence of at least two cell lines that are genetically different in the same individual. Can be germinal or somatic. If somatic, you find cell lines that are genetically different in different tissues of body. If germinal, can lead to children having AD condition while neither parent is affected.

Question 9

Autosomal recessive

Answer 9

Horizontal transmission; both sexes pass it on; M/F equally affected; more common in consanguineous parents; complicated by ethnic associations or locus (genetic) heterogeneity

Question 10

X-linked inheritance

Answer 10

Males almost always affected (hemizygous for X) while females typically carriers. If XL is lethal to males, only females seen with disease. Only passed on by females. Males affected more. About 2/3 of mothers with affected boys are carriers.

Question 11

Y-linked inheritances

Answer 11

Only males pass on and only males affected. Vertical transmission.

Question 12

Mitochondrial inheritance

Answer 12

Vertical transmission; transmission only through females.. High penetrance. Parents usually affected.

Question 13

Trinucleotide repeat disorders

Answer 13

Display anticipation (earlier appearance and increased severity of disease in successive generations). REpeats form due to DNA slippage resulting in either an increase or decrease in number of repeat copies. Usually autosomal dominant.

Class 1: repeat in 3’ untranslated region, higher risk with maternal transmission
Class 2: repeat is translated, higher risk with paternal transmission. Excessive length leads to misfolded proteins (e.g. Huntington’s)

Question 14

Hardy-Weinberg equation

Answer 14

p^2+2pq+q^=1; p+q=1
p = freq of A in population
q= freq of a in population
p^2 = freq of AA
q^2= freq of aa
2pq= freq of Aa

Question 15

Frequency of an XL condition in males =
Frequency of carrier females =
For XL recessive conditions with lethal mutations, __ of sporadic cases are due to ___.
Mother has a ___ chance of being a carrier if there is only one sporadically affected male

Answer 15

• Recessive allele frequency
• = 2pq
• 1/3; new mutations
• 2/3