Autosomal Dominant And Recessive Disorders And Factors That Complicate Inheritance Patterns

Question 1

T/F phenotype is a result of interaction of genotype and environmental factors

Answer 1

T

Question 2

Proband

Answer 2

. Arrow

. Denotes 1st individual diagnosed in pedigree

Question 3

First degree relatives

Answer 3

. Related at parent-offspring or sibling level

Question 4

Second degree relationship

Answer 4

Relatives are removed by 1 additional generational step

. Grandparents-grandchildren, uncle-nephew

Question 5

Third degree relationship

Answer 5

. First cousins

. Great grandchildren

Question 6

Allele

Answer 6

. Alternate forms of a gene
. One inherited from mom and one from dad
. Can be identical to each other or not

Question 7

Autosomal dominant inheritance

Answer 7

. Vertical transmission
. No skipped generations 
. Equal proportions of genders 
. Father-son transmission possible 
. Example: postaxial polydactyly, Huntington’s, Marfan’s, neurofibromatosis type 1, retinoblastoma

Question 8

Characteristics of autosomal dominant inheritance

Answer 8

. Heterozygous less severe than homozygous
. Spontaneous mutations common
. Trait shows variation in expression
. Basic defect tends to involve structural protein
. Sex-limited disorders do exist
. In determining risk, which parent is affected is inconsequential

Question 9

Autosomal recessive inheritance

Answer 9

. Horizontal transmission
. Skipped generations
. Equal proportions of genders
. Father to son transmission possible
. Fairly uncommon
. Usually result of 2 heterozygous parents
. Examples: sickle cell, CF, hurler syndrome
. Prevalence of affected offspring is 25%
. High prevalence of rare recessive disease suggests consanguinity

Question 10

Tyrosinase-negative albinism

Answer 10

. Autosomal recessive disease

. Mutations in gene encoding tyrosinase causes metabolic block in melanin pigment synthesis

Question 11

Consanguinity

Answer 11

Mating of closely related individuals

Question 12

Achondroplasia

Answer 12

. Autosomal dominant disorder
. Heterozygous have reduced stature but normal life span
. Homozygous usually die in infancy from respiratory failure

Question 13

penetrance

Answer 13

. Probability that a mutant genotype will have any phenotypic expression at all
. Measured as percentage of persons w/ mutant genotype who are actually affected
. Reduced means fewer than 100% individuals w/ mutant genotype are affected

Question 14

Retinoblastoma

Answer 14

. Autosomal dominant
. Malignant eye tumor that a rises from mutation in tumor suppressor gene
. 1/20,000 children affected
. Penetrance is 90% so 10% individual w/ mutant genotype are phenotypically normal but still have 50% chance of producing affected child
. In order to how the tumor, one must have mutant genotype AND experience a gene-damaging event in normal homologous chromosome in order for it to occur
. Inherited as autosomal dominant, expressed only when autosomal recessive where both copies are mutated from inheritance of environmental damage

Question 15

Neurofibromatosis type 1

Answer 15

. Most common autosomal dominant disorder
. 1/3,000 individuals
. Some people have only a few spots, others have nerve tumors
. Less than 10% of people develop malignancies
. Expression can vary in offspring, mildly affected parent can have severely affected offspring
. Penetrance is 100%

Question 16

Huntington disease

Answer 16

. Autosomal dominant disease w/ delayed age onset
. 1/20,000 people w/ 100% penetrance
. Presents at 30-50 y/o, onset to death is 15 yrs
. Causes progressive loss of motor control and psychiatric disorders
. All cases are inherited, hardly ever spontaneous mutation
. Mutation: expansion of trinucleotide region (CAG) in 5’ untranslated region of gene

Question 17

Pleiotropy

Answer 17

. Genes that exert effects on multiple aspects of physiology or anatomy

Question 18

Marfan’s syndrome

Answer 18

. Autosomal dominant
. Affects eye, skeleton, and cardiovascular system
. 1/10,000 North Americans
. Caused y mutant gene for fibrillin causing excessively stretchy CT

Question 19

Locus heterogeneity

Answer 19

. Mutations at 2+ distinct loci can produce the same or similar phenotypes
. Single disease phenotype can be caused by many different mutations

Question 20

Osteogenesis imperfecta

Answer 20

. Autosomal disorder of type 1 collagen
. Causes bone fractures
. 1/10,000 children
. 100% penetrance w/ variable expression
. Mutations can occur in pro alpha-1 collagen or pro-alpha 2 collagen gene to alter the collagen triple helix

Question 21

Germline mosaicism

Answer 21

. Presence of more than 1 genetically distinct cell line in the germline but not in somatic cells
. Parent carries mutation in his/her germline but does not express disease in somatic cells
. This allows mutation to be transmitted to multiple offspring
. Relatively rare but can have significant effects on reoccurrence risks
. Sign this is happening is when multiple offspring present with an autosomal dominant disease and there is no family history
. Causes osteogenesis imperfecta type II, muscular dystrophy, hemophilia A, and some cases of achondroplasia and neurofibromatosis type I

Question 22

Genomic imprinting

Answer 22

. Differential activation of genes depending on the parent from which they are inherited

Question 23

Different effects of deletion of 3 to 4 Mb on the long rm of chromosome 15

Answer 23

. When deletion inherited by father is causes Prader-Willi syndrome causing short stature small hands and feet, and intellectual disability
. When inherited by mother is causes angelman syndrome causing severe intellectual disability, seizures, and ataxic gait