Genetics of Common disorders-with complex inheritane-Personalized Med

Question 1

Polymorphisms facts

Answer 1

1% of genome that separates us as people

can be small, or single

most are silent

small are functional and effect expression or activity of protein

Question 2

Mutation defintion

Answer 2

DNA change that severely alters activity or expression of gene

Question 3

SilentPolymorphism definition

Answer 3

Silent change in DNA that does not alter expression or activity of gene/protein

Question 4

Functional polymorphism defintion

Answer 4

subtle changes that alter levels of activity on gene-still in normal range
-somewhat diffferent but not completely different

Question 5

Relative risk

Answer 5

Pre of disease in relatives of affected person
/
Prevalence of disease in general population

Question 6

Heritiability-what it means and how to calc

Answer 6

(Variance in dizygotic pairs-variacne in monozygotic pairs)/variance in dizygotic pairs

0-trait not due to heritability
1-trait is due completely to heritability

Question 7

Genetic linkage analysis

Answer 7

Marker co-segregates with disease

Can say mutation is somewhere near to marker

Then sequence genes in area and look for mutation of family/different families, then confirmm mutation affects expression or activity of gene

Question 8

Deep resequencing of human genome

Answer 8

Next gen sequencing allows identification of rare/individual mutations because so fast and cheap

Question 9

HSCR

Answer 9

Hirschsprungs Disease

Neural crest defect for cells that go on to form enteric nervous system
-mutations in receptor/ligand needed for neural crest migration

Enlarged colon with no nerves

Complex hereditary

• males 2x more likely than females w/i fam
• MZ does not show perfect concordance

Found 3 alleles that somehow, together make disease

Question 10

Phenotypic overlap of MS, survival bone marrow transplant, T1 diabetes

Answer 10

Autoimmunity

Question 11

Phenotypic overlap of schizo, autism, biopolar

Answer 11

neurodev disorder

Question 12

Multifactorial defintion and evidence

Answer 12

Refers to inheritance of phenotypic trait that is attributale to two or more genes and/or epigenetic

not simple recessive/dom
twin studies

Question 13

Polygenic defintion and vs…

Answer 13

Character determined by combined action of number of genetic loci vs monogenic

Question 14

Risk for genetic common/rare disease

Answer 14

functional polymorphism

mutations

Question 15

Risk for epigenetic diseases

Answer 15

covalent mods to DNA or chrom

Influenced by non-genetic environmental factors

Question 16

definitions for rare/common disease

Answer 16

common=5%=less phenotypic effect but effect more population

rare-significant phenotype bu lesson general population

Question 17

Association studies for common variants

Answer 17

if polymorphism is co-ineritbed with disease alley, then the polymorphism should be inherited more frequently in individuals with disease
-other WT nucleotide where polymorpishm is should be inherited more often by unaffected siblings

Question 18

GWAS-how to do and problems

Answer 18

Recruit many with disease

Isolate DNA and genotype whole genome

Stats-identify SNP allele coinherited with disease

Problems with reproducibility and functionality

Question 19

How are Snps inhierted

Answer 19

in blocks

Question 20

ENCODE project

Answer 20

Determined 80% of genome is involve din at least one biochemical event

99% of it is somewhat close to ENCODE identified event

Question 21

Far reaching expression methods

Answer 21

long distance promotoers, reg RNAs

Noncoding functional effects

Question 22

Epigenetic hypthesis

Answer 22

due to epimutations

non-genetic

interface between environment and gene expression

Heterogenous

Provide basis for heterogenity

Question 23

epigenetic technology (2)

Answer 23

IP CH3 DNA taken from indies ten hybridieed to DNA

Degree of hybridization indicates methylation status

Bisulfite seq-methylatio of particular DNA can then be determined by standard molecular approaches

many genes that lead to cancer have epigenetic alterations

Question 24

ommics

Answer 24

look at something-take expression pattern

parse into different subgroups that respond to dif pathways

metabolome-nice pocket-easy to target

sequence/find total amounts of whatever your looking at-see how patient is effected-what (omics thing) causes disease