Autosomal Recessive Inheritance

Question 1

Autosomal Recessive Inheritance

Answer 1

manifest in the homozygous state(2 mutant alleles)
Heterozygotes-1 mutant allele->healthy carrier
Offspring of heterozygotes have 1 in 4 chance of being homozygous-thus affected
Pedigree-horizontal transmission-affected typically seen in sibship of pro band
Affect both sexes equally
Male to male transmission
There may be consanguineous relations

Question 2

Autosomal Recessive-Recurrence

Answer 2

carrier by carrier
carrier by affected
affected by affected
carrier by normal
affected by normal

Question 3

Consanguinity

Answer 3

both parents of a child inherited the mutant allele from a SINGLE COMMON ANCESTOR

Question 4

Coefficient of Inbreeding (F)

Answer 4

probability that a homozygote has received both alleles at a locus from the same ancestral source.
PROPORTION OF LOCI AT WHICH A PERSON IS HOMOZYGOUS OR IDENTICAL BY DESCENT.

Question 5

Genetic isolates and inbreeding

Answer 5

Small groups that may have become separated from their neighbors by Geographic, religious, or linguistic barriers-FREQUENCY OF CERTAIN RARE RECESSIVE GENES IS MORE COMMON.

Question 6

Tay-Sachs disease

Answer 6

Rare, Recessive, but has incidence in small groups(genetic isolates)
Neuro degen disorder which is fatal in early childhood.
Ashkenazic Jews-100% times higher, 1 in 30
Hexamindase A, 4bp insertion, Deficient GM2 gangliosides, startle rxn, cherry red spot, deafness, progressive neurological degeneration.

Question 7

Sex-Influenced disorders

Answer 7

AR, expressed in both sexes at different frequencies. Ex. Hemochromatosis-more common in males-defective iron metal, enhanced iron absorption leads to iron overload with serious pathology

Question 8

Autosomal Dominant (AD)

Answer 8

manifests in heterozygous state-phenotype appears in every generation->VERTICAL TRANSMISSION-each affected person has an affected parent.
Exception: AD disorders can occasionally arise as a result of a new mutation.

Question 9

AD-Risk of inheritance to offspring if one parent affected

Answer 9

punnetts square-50%

Question 10

AD

Answer 10

each pregnancy is an independent event-after birth pregnancies remain 50%.
Usually affects both males and females equally.
Phenotypically normal family members do not transmit the disorder to children, with exception of incomplete penetrance

Question 11

AD-Osteogenesis imperfecta

Answer 11

AD, Collagen genes-Collagen type 1, Null/missense mutation, brittle bones, blue sclera, hearing loss, dental deformity.

Question 12

AD new mutations

Answer 12

New mutations can cause AD disorders.
Inverse relation b/w fitness of a given AD disorder and the proportion of patients who have new mutant genes. New mutations cause sig # of cases for NF1 and Achondroplasia

Question 13

Achondroplasia-

Answer 13

FIBROBLAST GROWTH FACTOR RECEPTOR-3 (FGFR3)
common, non-lethal form of chondrodysplasia
AD w/complete penetrance.
facies w/ frontal bossing and midfacehypoplasia, short stature w/normal trunk length, rhizomelic shortening of the limbs with trident hands and brachydactyly, avg intelligence w/ mild delay in motor development

Question 14

Marfan syndrome

Answer 14

FIBRILLIN GENE-abn fibrillin-1 monomers. building blocks of microfibrils->structural components of suspensory ligament of the lens and elastin in the aorta and other CTs.
DOMINANT NEGATIVE MUTATION->mutant fibrillin-1. SKELETAL ABNS, HYPERMOBILE JOINTS, OCULAR ABNS, CARDIOVASCULAR DISEASE. thin elongated limbs pectusexcavatum

Question 15

Sex-limited phenotype in AD

Answer 15

Preferentially expressed in only 1 sex.
Ex. Male-limited precocious puberty-familial testotoxicosis-boys undergo puberty at age 4. Look for male-to-male penetrance on pedigree

Question 16

Variability in phenotypic manifestations

Answer 16

Particularly characteristic in AD, but not restricted.
Reduced penetrance
Variable expressivity
Aging, other genetic loci, environment