lecture 6 Flashcards
are genetic crosses feasible for mapping genes in humans
Noooooo
why arent genetic crosses feasible for mapping genes in humans
controlled crosses not possible
mating couples generally produce a small number of offspring
Experiments would take many years to conduct
what could we use to map genes in humans
map a gene - conduct linkage analysis using molecular markers
what are molecular markers
small dna sequence differences like polymorphisms, within a species that are present at specific chromosomal location
gives position info
where are molecular markers present
throughout genome
do molecular markers have biological functions
most do not
no phenotype
do not affect phenotype
where are molecular markers seen
as bands on a gel
what can molecular markers be used to do
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
what are SSLPs
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
do ppl have same number of SSLPs
unrelated people likely have diff numbers of these repeats
humans have one set of paternal and one set of maternal sslps
how to determine lengths of sslps
lengths of regions can be detected by pcr amplification using primers binding to flanking sequences and resolving on a DNA gel
describe sslp pcr
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
what can function as dna fingerprints
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
what are short tandem repeats used for
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
what are SNPs
single nucleotide polymorphisms
how similar are human genomic sequences
2 genomic sequences of 2 unrelated people = 99.9% identical
most of 0.1% differences are single nucleotide variants = SNVs
what is classified as a SNPs
a variant must be found in at least 1 percent of any population, common among people, if not variant = could be mutation
where are SNPs common
common within a specific population or ethnicity
like ancestry or 23 and me = have info about SNPs
where are SNPs
could be in intergenic region
within a gene
or in a regulatory region near a gene
do SNPs affect health
most have no effect on health or development
do SNPs affect disease
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
how to map disease with snps
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
describe mapping a dominant gene with sslps
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
describe mapping of the CF gene by linkage analysis of molecular markers
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
describe the DNA marker haplotypes associated with the CF chromosomes carrying ΔF508
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
what is halotype
physical grouping of genomic variants or polymorphisms that tend to be inherited together as single group
describe early spread of cystic fibrosis
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
what is a reason why some mutations happen in some locations
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
describe when spanish colonized andes
spanish parents had hard time making kids
unlike natives = spanish had chronic mountain sickness = CMS
What genes enables the natives to flourish while lowlanders who move to high elevations suffer the
grave health consequences of CMS?
natives to high altitude regions such as tibetans genetically adapted to life at high elevation
describe hypothesis for tibet vs han chinese
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
describe method for tibet vs han chinese
compare tibetans to han chinese at over 500,000 snps across genome and look for differences
describe findings for tibet vs han chinese
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
describe SNPs and drug response, risk of disease, etc.
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
what is cms
condition caused by inability to obtain enough oxygen from the thin air of the mountains
