Corbett - Patterns of Single Gene Inheritance

Question 1

Hemizygous

Answer 1

X chromosome mutation in male (not homozygous since only one mutation, but not heterozygote since no second X chromosome)

Question 2

Allelic Heterogeneity

Answer 2

Different mutations in the same gene

Question 3

Phenotypic Heterogeneity

Answer 3

Different mutations in the same gene can produce different phenotypes (allelic heterogeneity where DIFFERENT phenotypes result)

Question 4

Locus Heterogeneity

Answer 4

Mutations at DIFFERENT locii produce the SAME phenotype (i.e. mutation in K+ regulation gene or Na+ regulation gene can both cause symptoms of inhibited Na+/K+ channels)

Question 5

Autosomal Recessive Disorder

Answer 5

Must be bb, can be compound heterozygote. Often reduce/eliminate function of gene product, rare. Chance of bb is 1/4, chance of carrier Bb is 2/4. Chance of unaffected carrier is 2/3.
Increased risk: Carrier frequency, consanguinity, inbreeding.
Identifying pedigree: Parents unaffected, males=females, 1/4 kids ratio, yes male–>male transmission, increased risk due to inbreeding

exs: Cystic Fibrosis, Tay-Sachs, Sickle Cell

Question 6

Autosomal Dominant Disorders

Answer 6

50% mendelian disorders, high incidence. Since BB is rare, Bb is diseased, bb is fine, Bb x bb = 1/2 affected risk. No carriers since Bb is affected.
Key to pedigree: MUST have affected parents, male = female, yes male–>male transmission, normal kids have normal kids

Question 7

Incomplete Dominance

Answer 7

BB has worse symptoms than Bb. “Red” and “Pink” flowers. Ex: Achondroplasia, Familial Hypercholesterolemia. BB is rare like in Autosomal Dominance

Question 8

X-linked inheritance (recessive)

Answer 8

If mom carrier, 1/2 risk of son symptoms,1/2 risk of daughters being carrier. If dad is carrier, all daughters are carriers, all sons are unaffected.

Pedigree: NO MALE–>MALE. Almost exclusively males affected. Chance of women being affected despite XnXs due to somatic mosaicism, unbalanced X-inactivation. Can “skip generations” due to female carriers.

Ex: Duchene Muscular Dystrophy

Question 9

X-linked Dominant

Answer 9

Female “carriers” are disease phenotype. NO MALE–>MALE. So more female than male affected (since women get 2 X chromosomes)

Question 10

Mendelian Exceptions (9)

Answer 10

1) Penetrance
2) Expressivity
3) Sex-limited
4) Germ line mosaicism
5) Genetic Imprinting
6) New Mutations
7) Misattributed Paternity
8) Mitochondrial Inheritance
9) Trinucleotide Expansion

Question 11

Reduced Penetrance

Answer 11

Not 100% of people with mutation have phenotypic expression. Can be age dependent

Question 12

Variable Expressivity

Answer 12

Same disease genotype can have variable phenotype (i.e. 100% of bb are affected, but some get itchiness, some get full body rash..)

Question 13

Sex-Limited traits

Answer 13

Autosomal mutation, occurs in both sexes, but only one sex expresses phenotype, due to anatomical/physical differences
Pedigree: can see affected kids from unaffected parents, YES MALE–>MALE so excludes X-linked
Ex: Male-limited precocious puberty is AD mutation in luteinizing hormone receptor gene, only seen in males. Hemachromatosis, pregnant women have better iron reduction so see symptoms more in men.

Question 14

Mosaicism (Germ line and Somatic)

Answer 14

Somatic: early developmental mutation causes disease phenotype in somatic tissue

Germline: “ + affects gametes, so see diseased kids from healthy parents who aren’t even carriers!

Question 15

Genomic Imprinting

Answer 15

Can cause AR disease in Bb despite heterozygosity, or no AD disease in Bb despite B gene. Imprinting reverses after one generation, so can have diseased grandma–>unaffected son–>diseased kid, all Bb. Ex: Prader-Willi vs. Angelman

Question 16

Compound Heterozygote

Answer 16

Both alleles mutant, but mutations are at separate location in gene