Biochem Exam 2

- Postaxial polydactyly

- Marfan syndrome

- Neurofibromatosis type 1

- Retinoblastoma

- Huntington disease

- Vertical transmission

- no skipped generations

- equal proportion of genders

- may show father to son transmission

- 50% of offspring from affected individual will also be affected

- unaffected individuals do NOT have affected offspring

- Aa is less severe than AA

- Spontaneous mutations are common

- the trait frequently shows variation in expression

- the basic defect tends to involve a structural protein

- Sex-limited disorders DO exist

- In determining risk, which parent is affected is inconsequential

- Horizontal transmission

- skipped generations

- equal proportion of genders

- may show father to son transmission

- 25% of offspring from affected individual is also affected

- a high prevalence of a rare autosomal recessive disease suggests consanguinity

- cystic fibrosis

- sickle cell disease

- Hurler syndrome (a lysosomal-storage disease)

- tyrosinase-negative albinism

- achondroplasia

The probability a mutant genotype will have any phenotypic expression at all. It is measured as the percentage of people with a mutant genotype that are actually affected.

- Reduced penetrance (<100% penetrance)

- Delayed age onset

- Variable expression

- Pleiotropy and Heterogeneity

- New mutation

- Germline mosaicism

- Genomic imprinting

= Increased risk of thrombosis

Heterozygotes (4-7% of general population)

- 5-7 times greater risk for DVT

Homozygotes (0.06-0.25% of general population (up to 10% in S. Sweden and Greece))

- 80 times risk for DVT

The degree of severity of a given mutant phenotype or disease and can range from so mild that the affected person is unaware of it to an extremely severe disease state.

Variable expression- refers to the extent of expression of the particular disease phenotype

where more recent generations display more severe forms of an inherited disease

- an X-linked dominant condition

• - CGG repeats in 5'-UTR of FMR1 gene
• (6-50 copies = Normal, 50-230 copies = Normal transmitting males, 230-1000 copies = Fragile X Syndrome)

- Exhibits anticipation

- NTM cannot transmit the disease to their daughters, but expansion of copies is seen through the daughters, and is represented in their offspring

- These expansions do NOT occur in male transmission

- Most common inherited form of mental retardation in males

- Penetrance = 80% for males, 30% for females

- >230 copies of CGG repeat = methylation of FMR1 (stops expression of gene) = no FMRP product = Fragile X Syndrome

One X chromosome in every somatic cell at the 16-64 cell stage of X females is randomly and permanently inactivated in that cell and in all its clonal descendants

- twice as many affected females as males

- NO father to son transmission

- Vertical transmission with no skipped generations

- occurrence/recurrence depends on the affected parent's gender

- Fragile X Syndrome

- Hypophosphatemic rickets

- incontinentia pigmenti type 1