Genetic Variation- Chromosomes, Sequence, and Variation

Question 1

Genetics

Answer 1

relating traits we care about to variation in the genome

Question 2

Majority of genome is

Answer 2

not protein-encoding; minuscule amount of genome codes for protein compared to rest of genome

Question 3

Alleles

Answer 3

sequence variation at a site in the genome; mammalian genes both have maternal and paternal allele

Question 4

single nucleotide polymorphisms

Answer 4

SNPs; these are type of genetic variability located throughout genome; single base pair difference in sequence of different chromosomes in population 1/200 bp on average; discovered by sequence alignment

Question 5

heterozygous for SNP

Answer 5

overlap of A and T at same position; chromatogram intensity often 1/2 height (bc only have templates have A or T nucleotide); paternal and maternal inherited chromosomes are different

Question 6

human genome size and autosome #

Answer 6

3.2Gb, 22 autosomes

Question 7

mouse genome size and autosome #

Answer 7

2.6Gb, 19 autosomes

Question 8

Dog genome size and autosome #

Answer 8

2.41Gb and 38 autosomes

Question 9

Horse genome size and autosome #

Answer 9

2.7Gb, 31 autosomes

Question 10

chimp genome size and autosome #

Answer 10

3.3Gb, 22 autosomes

Question 11

cat genome size and autosome #

Answer 11

2.7 Gb, 18 autosomes

Question 12

cow genome size and autosome #

Answer 12

2.87Gb, 29 autosomes

Question 13

Why are sequence variations pervasive in genome

Answer 13

genome is encoded in physical molecules so it is subject to damage from chemically reactive species, repair failures, and copying mistakes; elements in genome are capable of self replication -> sequence changes

Question 14

transposable elements

Answer 14

active elements within the genome that are capable of self-replication -> sequence changes to the genome

Question 15

Variation in genome effect

Answer 15

genes must have correct sequence for proper function; some changes dnt impact fx others reduce or destroy ability of gene to carry out role in cell and body; impact on fx -> affect on phenotype

Question 16

SNP creation

Answer 16

damage not repaired properly and when DNA pol incorporates wrong nucleotide when copying genome

Question 17

SNP in mitosis

Answer 17

some somatic body cells will differ from others

Question 18

SNP in meiosis

Answer 18

“non-Mendelian event”; resulting offspring will differ from parent

Question 19

SNP alleles

Answer 19

usually just 2 though 3 can happen; more frequent allele= major allele, less frequent allele= minor allele; which is major and which is minor can differ based on sample studied

Question 20

“Fixed” for a given allele

Answer 20

A breed where only this allele is found never the other (ie if G and A allele and only find G allele in quarter horses never the A the QHs would be fixed for G allele)

Question 21

private allele

Answer 21

2 alleles found in one breed but all other breeds only have one of those alleles so the second allele would be private to that breed (ie Shetland ponies have A and C alleles but all other horses only have A allele so C allele is private to Shetland pony)

Question 22

SNP useful for maping

Answer 22

mutate at low rate compared to other sequence variants; also typically only two allele

Question 23

Manhattan plot

Answer 23

map phenotypes of interest; use these for Genome wide association mapping studies (look at position of SNPs vs test value); simple plots for things like eye color harder with things with multiple factors such as body mass

Question 24

SNP discovery

Answer 24

discovered by sequence alignment

Question 25

How to calculate allele freqency

Answer 25

of “X” allele chromosomes/ (total # of case chromosomes)

remember to multiply # cases studied by 2 for total # case chromosomes because 2 chromosomes/ case
remember heterozygous will have 1 allele per case homozygous will have 2 or 0 depending on if you are examining dominant or recessive

Question 26

Genome wide association mapping studies

Answer 26

genotype 10k-1M SNPs throughout genome; presence of each SNP is tested for association with a trait; looking for connection btwn phenotype and allele frequency at positions

Question 27

polygenic

Answer 27

aka complex traits; multiple genes and environmental factors all contribute to make the trait value; vast majority of traits are complex; often are qualitative traits measured on continuum not yes no
ex. body condition

Question 28

rhythmic motor behaviors in nature

Answer 28

• breathing
  -locomotion
  -stridulation
• insect flight
  Gate change (rhythmic motor behavior change in horses) due to a SNP in gene DMRT3 (Icelandic points Tolt); if mice have SNP change to DMRT3 gene (transcription factor) then they too have gate change

Question 29

other variables in gate

Answer 29

• limb length
  -length of neck
• length of back
• center of gravity
  these are all biomechanics showing interplay btwn SNP and biomechanics

Question 30

SNP in cattle

Answer 30

causes leukocyte adhesion deffect in PM expressed protein (lack of leukocyte B2 integrin expression); all those with mutant allele related to one bull who sired a ton of calves via artificial insemination

Question 31

maincoon cat familial hypertrophic cardiomyopathy

Answer 31

linked to SNP (cardiac myosin binding protein)

Question 32

Indel variations

Answer 32

insertion or deletion that leads to difference in presence of absence of small or large stretch of sequence; less common than SNPs but can exert dramatic impacts on gene fx if occur in coding exon (especially if -> frameshift); some are v large and contain entire genes or pieces of genes or regulatory sequences for genes

Question 33

copy number variations

Answer 33

CNVs/ strucutral variations/ copy number polymorphysms= large scale < 1kb differences in genome content; bias for effecting non-genetic sequences but effect genetic sequences as well; CNV is pervasive in genomes

Question 34

alignment display convention with indels

Answer 34

put in *** for gap where insertion is in genes without insertion so they line up in computer though this is not what they look like in reality

Question 35

what came first with indel

Answer 35

usually we can’t know which is ancestral state and which state is from insertion or deletion so not helpful for ancestral tracing

Question 36

myostatin gene whipits

Answer 36

have 2 nucleotide sequence variation in myostatin gene due to indel inactivating myostatin gene (frameshift -> premature truncation of protein); if heterozygous run faster but if homozygous for mh/mh have too much muscle and slower with debilitating muscle cramps

Question 37

microsatellites

Answer 37

short stretches of repeated sequence aka simple tandem repeats; DNA pol frequently makes mistakes when copying these repeats especially if track is long and simple; markers not used for mapping studies; sometimes they are direct cause of phenotype variation

Question 38

microsatalites vs SNPs

Answer 38

microsatalites mutate at a higher rate; many alleles at each marker so they are highly informative though not used for mapping studies; easy to genotype by measuring length differences; amenable marker for genome wide scans; high mutation rate obscures relationship among alleles in population (many alleles identical by state but not by descent)

Question 39

epilepsy

Answer 39

caused by small satellite repeats in some cases; look at PCR of this and can see repeats increase or decrease length of sequence; diff in length of primer gives rise to DNA products; homozygous and heterozygous get diff PCRs bc diff repeats lengths

Question 40

CNV in sharpeis

Answer 40

more CNVs in chormosome 15 -> wrinkly face but also to periodic fevers but some healthy sharpeis have just as many CNVs showing impact of other genetic modifiers on how clinical phenotype being expressed

Question 41

coat color variation in horess

Answer 41

from 4.6kb duplication (strong genetic singal highly correlative for this)

Question 42

Mobile elements

Answer 42

interspersed repeats sequences and transposable elements can move themselves within genome and propagate independent of cellular replication; most are fixed for the insertion (all chromosomes in species carry the insertion) but some -> allele differences (segregating for insertion/ non-insertion); ubiquitous; account for substantial quantity of genetic material

Question 43

phenotype mobile genetic elements

Answer 43

mobile genetic elements can -> phenotype change

Question 44

narcolepsy doberman

Answer 44

caused by gene disruption via short interspersed element (type of transposon) of gene that codes for GCPR

Question 45

Chondrodysplasia in domestic dogs

Answer 45

retrotransposon is associated with breed-defining chondysplasia in domestic dogs (FgF4 retrogene)

Question 46

transposable elements

Answer 46

endogenous viruses; these = mobile elements

Question 47

intervertebral disk displacement

Answer 47

example of retrotransposons encoding fibroblast growth factors; also shown in some skeletal deformations in humans; this is bc of diff patterns of growth factors

Question 48

Long interspersed elements (LINE), short interspersed elements (SINE)

Answer 48

retrotransposons that exist at high copy in mammalian genome; these can integrate into gene disrupt it and cause change in phenotype; 1/2 of all annotated canine genes contain SINE repeats

Question 49

merele patterns in domestic dogs

Answer 49

from retrotransposon insertion (SILV); heterozygous is merel homozygous recessive is white

Question 50

Canine transmissible venereal tumor

Answer 50

associated with LINE insertion bc oncogene

Question 51

genomic DNA sequences differ between

Answer 51

species, breeds, sub-populations, individuals

Question 52

sequence differences (markers) w in individuals of a species can be used to

Answer 52

map traits

Question 53

most sequences variation function

Answer 53

no apparent function

Question 54

sequence variations contributing to trait differecnes

Answer 54

have clinical relevance such as disease

Question 55

phenotype/ dx causing mutations an be

Answer 55

SNPs, indels, and many other kinds variations