Complex Inheritance & Population Genetics Flashcards
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.
Reference genome
Common
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.
GRCh37
hg19
GRCh38/hg38
T2T
_____ diseases are caused by a mutation on one gene (cystic fibrosis)
_____ diseases are caused by variations on multiple genes (coronary artery disease)
Monogenic
Polygenic
_____ model #1 is used for single gene diseases. They are used in ___ diseases with relatively ____ sibling recurrence.
Mendelian
Rare
High
____ model #2 is used for diseases caused by multiple genes. Disease frequency is more ___ and sibling recurrence is relatively ___.
Example: diabetes, schizophrenia, and MS
Multifactorial
Common
Low
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.
Phenotype
Distribution of risk
____ inheritance: actions of multiple different loci, May be polygenic and/or may have environmental inputs acting on a genetic susceptibility
Examples: asthma, diabetes, clefting
Complex
Multifactorial phenotypes may be either ____ or ____
Quantitative
Qualitative
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.
Cluster
Inheritance
The risk for neural tube defects and other Multifactorial traits are based on ___ ___ rather than calculations.
Empirical data
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 ____%
Degrees of Relationship
3 -5
2
0.5
Risk of schizophrenia among the relatives of individuals with schizophrenia versus Mendelian expectations:
The ___ ___ method is a powerful design for ruling in or out genetic contribution to a phenotype. ____ (MZ) twins are compared to ___ (DZ) twins
Twin study
Monozygotic
Dizygotic
MZ twins have ____ in common genes.
DZ twins have _____ in common genes.
100%
50%
Graph comparing DZ to MZ concordances for schizophrenia:
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 __ ____.
Blocks
Linked
In linkage
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
Haplotype
Near
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.
Linkage disequilibrium
Linkage disequilibrium
Certain alleles tend to occur ____ due to being close on a chromosome (haplotype)
Together
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.
Patterns
Greater diversity and longer time recombining alleles leads to ___ LD blocks.
Smaller
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.
Hypothesis
Genome
Association of specific allele or haplotype in GWAS studies is expressed as ___ ___ (OR) or ___ ___ (RR) >1.
Odds ratios
Relative risks
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.
Marker
A positive hit ___ ___ mean the gene is necessarily disease relevant
Does not
Type 2 diabetes:
Identified ____ loci with significant association. ____ genes with associations attributable to coding variants potential therapeutic targets
243
18
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.
Common
Containing
Take home:
____-____ ___ 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
Hardy-weinberg law
Hardy - Weinberg Equilibrium:
q is relatively small compared to p, so when q2 < 1/100, we can assume that p equals ___ and 2pq equals ____
1
2q
The basic constructs of p and q can be used to calculate genotype frequencies when these main assumptions are made:
The population is large, mating is random, the allele frequencies remain constant within the population
HW most commonly answers these questions:
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
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.
2/3
If two heterozygous parents, the probability of being affected is ____ for autosomal recessive disease
1/4
The risk of this individual having an infected offspring = (2/3) x (risk partner is a carrier) (1/4)
= _____ from HW
2pq
Exceptions to large population/random mating:
____ ____ or ___ ____ is when meeting generally occurs within subgroups of a population
Population stratification
Isolated populations
____ ____ is choosing to mate with a similar characteristics. Could be based on a condition. Can include general physical characteristics, are personality traits.
Assortative mating
_____ is choosing a mate who is biologically related. More likely to carry the same recessive alleles, because of shared common ancestors.
Consanguinity
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
Genetic drift
migration/gene flow
Take homes:
Examples of diseases with a higher frequency in certain populations, due to genetic drift:
- Tay-Sachs disease common in Jewish population
- MSUD in Pennsylvania Plain Mennonites
- Glutaric acidemia and Propionic Acidemia in Amish
