Genome Variation

Question 1

what effects diversity in a population

Answer 1

genetic bottlenecks reduce diversity - reduced population to breed from

mutation promotes diversity

Question 2

how do mutation rates change, and how many mutations do we normally have

Answer 2

mutation rate rises with paternal age
non-germline mutation rates are 20x higher
estimated 70 mutations with each diploid human genome

Question 3

what are genetic variations in a population caused by

Answer 3

exogenous factors - radiation, chemicals, mostly somatic

endogenous - segregation - aneuploidies
recombination - translocation errors
DNA replication errors
inadequate repair mechanism

Question 4

what are the two classes of genetic variation

Answer 4

variation that does not alter DNA content such as single nucleotide replacements or balanced translocations/inversions

variations that result in net loss or gain of DNA sequence
can be while chromosome or single nucleotide

Question 5

what is neutral variation

Answer 5

small scale mutations that don’t alter genome

Question 6

what were 5 studies used to identify human genome variation

Answer 6

The human genome project 2003 (24 chromosomes, 1-22, X, Y, 20,000 + genes and 3mil subunits 3Gb)

the HapMap Project - haplotype map of genome

The 100 genomes project, 2008

The welcome trust

Genomics england

Question 7

what are 4 specific types of genetic variation

Answer 7

SNP’s - single nucleotide polymorphisms - C to T is most common (90% of variations)

SNV’s - single nucleotide variants (rare variant)

indels - insertion or deletion of one or more nucleotides - these can occur at restriction sites ( restriction fragment length polymorphism)

CNV’s (copy number variants, 0.1%) more than 100 nucleotides in length

Question 8

what is the impact of variation frequency

Answer 8

SNV’s most abundant type - the variation is dependant of the impact of variation on the phenotype ie larger impact in phenotype he less frequent

Question 9

what is an SNP and what are the subtypes

Answer 9

single nucleotide variation in the genome differs between members of the same species
predominantly C and T alleles - common genotypes CC, CT, TT

intronic/intergenic variants - between genes or exons ie as they occur in introns they don’t matter

coding/extronic - missense mutation (aa change), non-sense mutation (premature stop) and silence mutation

Question 10

what are microsatellite simple repeats

Answer 10

VNTR’s - short tandem repeats or simple sequence repeats

unstable and prone to replication slippage - variable, can cause disease but subject to where it is expressed within the genome

Question 11

what are CNV’s

Answer 11

4.8-9.7 of human genome contributes to CNV’s, distributed in subtelomeric and peritelomeric regions

Question 12

what types of gene groups have enriched CNV repeats

Answer 12

immune response, drug metabolism, olfactory receptor genes
T cell receptor genes (needed variations for VDJ recombination and defence)
protein phosphorylation, signal transduction, degradation

Question 13

what is negative selection

Answer 13

most variation is neutral - no effect
mutations that are strongly deleterious will be elating by natural (negative selection)
mutations with lat onset are not subject to negative election and can be more frequent
mutations that show early on will not persist in the population

Question 14

what 3 forces govern variation to occur

Answer 14

selection reduces diversity
positive selection of SNV’s
positive selection of CNV’s

Question 15

how does selection reduce diversity

Answer 15

positive selection for gene variations

reduced diversity is shown in regions with selective pressure

Question 16

how do positive selection of SNV’s affect variation

give an example

Answer 16

DNA variation that produces selective advantage - increases in frequency in a population
FOXP2 - regulates neural motor control of the orofacial regions and vocalisation - mutation sin this are associated with speech and language disorders which greatly reduce passing on mutation

Question 17

how does positive selection of CNV’s affect variation in a population using an example

Answer 17

high AMY1A copy number is thought to be beneficial adoption that is spread as human diets increases become rich in insoluble starch

Question 18

what are the stats for variation between human genetic variation

Answer 18

most variation is found within populations and only an additional 10% of variation is found between populations

people are most similar to members of other populations than tomemeblrs of their own populations

Question 19

where are rare variants more common

Answer 19

more common to one population

Question 20

how does population history impact variant frequency profile

Answer 20

recent bottlenecks have low frequency variants

all population shave enrichment of rare variation demonstrating recent explosive population expansion