lecture 6

Question 1

are genetic crosses feasible for mapping genes in humans

Answer 1

Noooooo

Question 2

why arent genetic crosses feasible for mapping genes in humans

Answer 2

controlled crosses not possible
mating couples generally produce a small number of offspring
Experiments would take many years to conduct

Question 3

what could we use to map genes in humans

Answer 3

map a gene - conduct linkage analysis using molecular markers

Question 4

what are molecular markers

Answer 4

small dna sequence differences like polymorphisms, within a species that are present at specific chromosomal location
gives position info

Question 5

where are molecular markers present

Answer 5

throughout genome

Question 6

do molecular markers have biological functions

Answer 6

most do not
no phenotype
do not affect phenotype

Question 7

where are molecular markers seen

Answer 7

as bands on a gel

Question 8

what can molecular markers be used to do

Answer 8

map a gene - like a disease causing gene
by determining the linkage between the gene of interested and a molecular marker = linked to gene of interest

Question 9

what are SSLPs

Answer 9

simple sequence length polymorphisms
human genomes have much repetitive dna, including multiple repeats of short, simple, dna sequences called sslps at specific locations of the genome

Question 10

do ppl have same number of SSLPs

Answer 10

unrelated people likely have diff numbers of these repeats
humans have one set of paternal and one set of maternal sslps

Question 11

how to determine lengths of sslps

Answer 11

lengths of regions can be detected by pcr amplification using primers binding to flanking sequences and resolving on a DNA gel

Question 12

describe sslp pcr

Answer 12

paternal and maternal = 2 since one from each parent
do pcr
maternal is longer = more repeats of sequences
dad = few repeats, amplify and determine size and which came from each parent

Question 13

what can function as dna fingerprints

Answer 13

patterns produced on gel by sslps at the multiple locations of the genome can function as DNA fingerprints
chances of multiple markers having same repeat = slim unless family
can determine how closely related to a person

Question 14

what are short tandem repeats used for

Answer 14

us databases for violent unsolved crimes
collect and pcr amplify markers and get pattern of sslps
distant cousins of the criminal likely share some of those markers
blood dna testing = like if relative donates blood ot something, totally by chance
but chance of having all the sam repeats = very low

Question 15

what are SNPs

Answer 15

single nucleotide polymorphisms

Question 16

how similar are human genomic sequences

Answer 16

2 genomic sequences of 2 unrelated people = 99.9% identical
most of 0.1% differences are single nucleotide variants = SNVs

Question 17

what is classified as a SNPs

Answer 17

a variant must be found in at least 1 percent of any population, common among people, if not variant = could be mutation

Question 18

where are SNPs common

Answer 18

common within a specific population or ethnicity
like ancestry or 23 and me = have info about SNPs

Question 19

where are SNPs

Answer 19

could be in intergenic region
within a gene
or in a regulatory region near a gene

Question 20

do SNPs affect health

Answer 20

most have no effect on health or development

Question 21

do SNPs affect disease

Answer 21

some snps - especially ones found within a gene or in a regulatory region near a gene = may play a role in susceptibility of a disease or sensitivity to an external factor
ex = like if in promoter region

Question 22

how to map disease with snps

Answer 22

2 closely located genes or markers eg snps = inherited together = if physically close together
eg = a disease causing gene and snp near the gene
scientists examine if specific set of snps always associate with disease = phenotype, maybe physically close to genes responsible for phenotype
if they do = means disease causing gene must be near by those snps

Question 23

describe mapping a dominant gene with sslps

Answer 23

collect dna samples from fam and pcr amplify with same primers and run on gel
mom and dad give certain patterns
large so causes disease = band migrates = diseased
they inherit allele = causes disease
could test embryo and prepare if they are diseased
depends how close marker is to gene

Question 24

describe mapping of the CF gene by linkage analysis of molecular markers

Answer 24

years of linkage analysis of molecular markers in many cf families
comparing normal vs cf individual on diff chromosomal locations
molecular cloning of gene
identification of 3 nucleotide deletion = loss of phe508 (CFTR)
first identify chromosome then narrow down

Question 25

describe the DNA marker haplotypes associated with the CF chromosomes carrying ΔF508

Answer 25

12 diff alleles, locations of cftr, hundreds of kb distance
1s and 2s inside coloured bars = schematic alleles of dna markers around the cftr gene = numbers on the right show counts of CF and normal chromosomes with dna marker halotypes = left
cftr gene tends to segregate together from one gen to next

Question 26

what is halotype

Answer 26

physical grouping of genomic variants or polymorphisms that tend to be inherited together as single group

Question 27

describe early spread of cystic fibrosis

Answer 27

bell beaker folk = probable migrating population responsible for the early dissemination of gene in europe
look at markers and location = molecualr snps are associated to common ethnic background

Question 28

what is a reason why some mutations happen in some locations

Answer 28

certain factors favour having this allele bc natural selection
helps better understand function of allele = sometimes for environmental reason
sickle ell anemia = bc resistance to malaria

Question 29

describe when spanish colonized andes

Answer 29

spanish parents had hard time making kids
unlike natives = spanish had chronic mountain sickness = CMS

Question 30

What genes enables the natives to flourish while lowlanders who move to high elevations suffer the
grave health consequences of CMS?

Answer 30

natives to high altitude regions such as tibetans genetically adapted to life at high elevation

Question 31

describe hypothesis for tibet vs han chinese

Answer 31

bc tibetans and chinese are closely related = snp variants must occur at a similar frequency in both groups
but if variant is associated with improved health at high elevation = specific variant frequency would have risen among tibetan = darwins natural selection

Question 32

describe method for tibet vs han chinese

Answer 32

compare tibetans to han chinese at over 500,000 snps across genome and look for differences

Question 33

describe findings for tibet vs han chinese

Answer 33

some snps in a gene called EPAS1 occur at v diff freq in tibetans = 87% and han chinese = 9%
EPAS1 regulates the number of rbcs that body produces in response to oxy level of tissues
allele selected for ppl who live at high altitudes

Question 34

describe SNPs and drug response, risk of disease, etc.

Answer 34

certain traits respond to drug
some well and other not well
helps determine traits = if patient will respond to therapy
need allelic info
now = do not have to map genes= have many advanced tools which can help determine

Question 35

what is cms

Answer 35

condition caused by inability to obtain enough oxygen from the thin air of the mountains