Diseases with Complex Inheritance

Question 1

Which class of genetic disease is most frequent at birth and after 25 years?

Answer 1

disorders with multifactorial inheritance

Question 2

Mendelian traits (and complex traits) are ______ or __________

Answer 2

qualitative aka continuous (like height) or dichotomous (present or absent)

Question 3

Complex traits result from contribution of _______ genes and with or without ___________ ___________.

Answer 3

multiple, environmental influences

Question 4

Quantitative traits are described by _________ distribution

Answer 4

Gaussian (like a bell curve). σ is the standard deviation of the mean, which is equal to the √variance.

Question 5

A theory of disease manifestation: many mutant genes must reach a threshold level for a that highly susceptible person to be diseased.

Answer 5

Polygenic Theory of Discontinuous Traits

Question 6

What is the relative risk ratio, λr?

Answer 6

a quantitative measure of the degree of familial aggregation of a disease ( from genetics usually, but families also share same environment)

λr= prevalence of the disease in the relatives of an affected person/ prevalence of the disease in general population

Question 7

Name three diseases that have a high risk ratio for siblings of diseased (because of familial aggregation).

Answer 7

Autism, type 1 diabetes mellitus, Crohn’s disease. Also MS and schizophrenia.

Question 8

What do case control studies entail when studying familial disease?

Answer 8

They compare the frequency of a disease in an extended family compared to a control family. Usually find that spouses and randos have a lower frequency of the disease.

Question 9

What is the proportion of alleles that you share with a second degree relative?

Answer 9

25% or 1:4

Question 10

There is greater concordance between _______ twins compared to _______ twins, showing a genetic component to inheritance of the disease.

Answer 10

monozygotic, dizygotic

Question 11

Quantitative traits’ variance (breath of the distribution) is related to genes and the _________. Vp is the ________ of a property and equals…

Answer 11

environment, variance, the sum of the variances (Ve+Vg)

Question 12

What is the “heritability of a trait”?

Answer 12

h^2, proportion of the total variance that is due to genes = Vg/(Vg+Ve)

Question 13

What is a V for monozygotic twins? Dizygotic?

Answer 13

Ve, Ve+Vg

Question 14

Digenic Retinitis Pigmentosa factors

Answer 14

no known environmental factors, 2 genes need to be mutant to cause photoreceptor death and blindness, 2 proteins associate and so both needed to reach threshold

Question 15

Hirschsprung Disease (HSCR)

Answer 15

Loss of a # of different genes can cause the disease (locus heterogeneity) so forms can be dominant, recessive, or multigenic. Can also be affected by variable expressivity and incomplete penetrance. Causes loss of ganglion cells, so decreased parasympathetic activity in the colon.

Question 16

Type 1 (insulin-dependent) diabetes (IDDM)

Answer 16

autoimmune disease that shows family aggregation (λr for sibling is 35) and concordance of 40% in MZ. A heterozygous HLA-DR cluster is in 95% of patients. Concordance of DZ varies based on how many DR haplotypes they have in common (1-25%)

Question 17

Idiopathic Cerebral Vein Thrombosis

Answer 17

A mutation in prothrombin 3
UTR mRNA results in a poor substrate for Protein C so it persists. Factor V can also be mutated as well as the prothrombin.

Question 18

Alzheimer rare Mendelian form

Answer 18

Inherited in a dominant manner, mutations in genes that encode precursor proteins creating insoluble aggregates, encode regulators of those precursors, and proteins that remove aggregates. Apolipoprotein E e4 allele increases risk for the disease 2 to 3 times more