Complex Inheritance & Population Genetics

Question 1

The ___ ____ is a patchwork assembly of different real human genomes collectively to represent the position sequence of the human genome. It’s not necessarily the most ___ allele in that position.

Answer 1

Reference genome
Common

Question 2

Currently ____ also called ____, from 2009 is the most commonly used clinically. Researches often use the updated ____/___, from 2013. ____ or telomere to telomere is a newly emerging reference.

Answer 2

GRCh37
hg19
GRCh38/hg38
T2T

Question 3

_____ diseases are caused by a mutation on one gene (cystic fibrosis)
_____ diseases are caused by variations on multiple genes (coronary artery disease)

Answer 3

Monogenic
Polygenic

Question 4

_____ model #1 is used for single gene diseases. They are used in ___ diseases with relatively ____ sibling recurrence.

Answer 4

Mendelian
Rare
High

Question 5

____ model #2 is used for diseases caused by multiple genes. Disease frequency is more ___ and sibling recurrence is relatively ___.
Example: diabetes, schizophrenia, and MS

Answer 5

Multifactorial
Common
Low

Question 6

In multifactorial inheritance, polygenic genes combined with environmental factors are responsible for the ____. This combination of multiple effects creates a ____ of ___ for a condition within a population.

Answer 6

Phenotype
Distribution of risk

Question 7

____ inheritance: actions of multiple different loci, May be polygenic and/or may have environmental inputs acting on a genetic susceptibility
Examples: asthma, diabetes, clefting

Answer 7

Complex

Question 8

Multifactorial phenotypes may be either ____ or ____

Answer 8

Quantitative
Qualitative

Question 9

Although Multifactorial traits or diseases tend to run in the family (____), there is no clear mode of ___ as there was for Mendelian traits and diseases.

Answer 9

Cluster
Inheritance

Question 10

The risk for neural tube defects and other Multifactorial traits are based on ___ ___ rather than calculations.

Answer 10

Empirical data

Question 11

What are the chances of having a child with a neural tube defect?
Based on ___ of _____:
In a first degree relative ____%
Second degree relative ____%
Third degree relative ____%

Answer 11

Degrees of Relationship
3 -5
2
0.5

Question 12

Risk of schizophrenia among the relatives of individuals with schizophrenia versus Mendelian expectations:

Answer 12

Question 13

The ___ ___ method is a powerful design for ruling in or out genetic contribution to a phenotype. ____ (MZ) twins are compared to ___ (DZ) twins

Answer 13

Twin study
Monozygotic
Dizygotic

Question 14

MZ twins have ____ in common genes.
DZ twins have _____ in common genes.

Answer 14

100%
50%

Question 15

Graph comparing DZ to MZ concordances for schizophrenia:

Answer 15

Question 16

Generic traits are inherited by ____. During Meiosis, crossing over between chromosome pairs is limited so chromosomes are inherited as blocks of sequence from ancestors. Alleles that are close together are ____ or __ ____.

Answer 16

Blocks
Linked
In linkage

Question 17

A ____ is a physical grouping of genomic variants (or polymorphisms) that tend to be inherited together. A specific haplotype typically reflects a unique combination of variants that reside ___ each other on a chromosome

Answer 17

Haplotype
Near

Question 18

In population genetics, ___ ___ (LD) is the non-random association of alleles at different loci in a given population. Loci are said to be in ___ ____ when the frequency of association of their different alleles is higher or lower than expected if the loci were independent and associated randomly.

Answer 18

Linkage disequilibrium
Linkage disequilibrium

Question 19

Certain alleles tend to occur ____ due to being close on a chromosome (haplotype)

Answer 19

Together

Question 20

Blocks of alleles are inherited together in ___ that depend on ancestry. Linkage disequilibrium blocks in one ancestry are not necessarily the same in another ancestry.

Answer 20

Patterns

Question 21

Greater diversity and longer time recombining alleles leads to ___ LD blocks.

Answer 21

Smaller

Question 22

Genome Wide Association Studies (GWAS) are ____-free studies of association between genetic variants and quantitative traits or disease. Associations are examined across the whole ___ using chip or sequencing techniques.

Answer 22

Hypothesis
Genome

Question 23

Association of specific allele or haplotype in GWAS studies is expressed as ___ ___ (OR) or ___ ___ (RR) >1.

Answer 23

Odds ratios
Relative risks

Question 24

Odds ratio or relative risks indicate the association between risk for the disease and the genetic ____ , such as a SNP allele. Probability of having the disease if the marker is present versus having the disease of the marker is not present.

Answer 24

Marker

Question 25

Question 26

A positive hit ___ ___ mean the gene is necessarily disease relevant

Answer 26

Does not

Question 27

Type 2 diabetes:
Identified ____ loci with significant association. ____ genes with associations attributable to coding variants potential therapeutic targets

Answer 27

243
18

Question 28

As GWAS analyses ____ variants (SNPs) usually typed on commercial SNP arrays they do not usually identify casual variants. GWAS identify common variants which are markers of a region of linkage disequilibrium ____ the casual variant.

Answer 28

Common
Containing

Question 29

Take home:

Answer 29

Question 30

____-____ ___ is most commonly applied to autosomal recessive diseases. It helps determine genotype frequencies from allele frequencies in a given population. It helps determine probability of carrier status for an AR disease

Answer 30

Hardy-weinberg law

Question 31

Hardy - Weinberg Equilibrium:

Answer 31

Question 32

q is relatively small compared to p, so when q2 < 1/100, we can assume that p equals ___ and 2pq equals ____

Answer 32

1
2q

Question 33

The basic constructs of p and q can be used to calculate genotype frequencies when these main assumptions are made:

Answer 33

The population is large, mating is random, the allele frequencies remain constant within the population

Question 34

HW most commonly answers these questions:

Answer 34

Calculate carrier frequency, calculate allele frequency for autosomal disorder from the disease prevalence in a population, or estimate the number of affected individuals from allele frequency

Question 35

An individual who is not affected, but has affected siblings, has a ____ chance of being a carrier. (both parents are inferred heterozygous). Three unaffected, allele combinations, and two of them are heterozygous.

Answer 35

2/3

Question 36

If two heterozygous parents, the probability of being affected is ____ for autosomal recessive disease

Answer 36

1/4

Question 37

The risk of this individual having an infected offspring = (2/3) x (risk partner is a carrier) (1/4)
= _____ from HW

Answer 37

2pq

Question 38

Exceptions to large population/random mating:
____ ____ or ___ ____ is when meeting generally occurs within subgroups of a population

Answer 38

Population stratification
Isolated populations

Question 39

____ ____ is choosing to mate with a similar characteristics. Could be based on a condition. Can include general physical characteristics, are personality traits.

Answer 39

Assortative mating

Question 40

_____ is choosing a mate who is biologically related. More likely to carry the same recessive alleles, because of shared common ancestors.

Answer 40

Consanguinity

Question 41

Exceptions to constant allele frequency:
1. Frequency of new mutation
2. Affects of the fitness
3. ___ ____ which is unpredictable and chance fluctuations in allele frequency. Examples include founder effect, and population bottlenecks.
4. ____/ ___ ___ is changes in allele frequency due to the slow diffusion of genes across a barrier

Answer 41

Genetic drift
migration/gene flow

Question 42

Take homes:

Answer 42

Question 43

Examples of diseases with a higher frequency in certain populations, due to genetic drift:

Answer 43

1. Tay-Sachs disease common in Jewish population
2. MSUD in Pennsylvania Plain Mennonites
3. Glutaric acidemia and Propionic Acidemia in Amish

Question 44

Answer 44