Recombination, Linkage & Gene mapping Flashcards
What are the two approaches to identifying genes?
Functional cloning & positional cloning
how does functional cloning identify genes
identify a gene by it’s product
what do you have to know in order to successfully do functional cloning
have some knowledge of its function
how does positional cloning identify a gene
by its location
Positional cloning uses markers to do what
to look for association of marker with phenotype which will show the genotype
if you see linkage b/w marker and disease you know what
disease must be in that area
is positional cloning family specific?
yes
when is positional cloning easier to use
mendelian disorders with predictable inheritance patterns
mapping the disease allele to specific marker position is what
positional cloning
what is used to find gene for achondorplasia
positional cloning
when does crossing over occur
prophase 1
there is at least how many recombinations per homologous chromosome pair
one
what is mendel’s second law
genes segregate independently of each other
for each gene, there’s two alleles, each one from where?
a different parent
what is linkage
the tendency for two different oci to be transmitted together as an intact unit through meiosis
linkage is opposing what?
mendel’s second law
mendel’s law is only true if what
linkage doesn’t occur
when is linkage analysis used
mapping genes
if there are parental types did recombination happen
no
if there are nonparental types did recombinatino happen
yes
what is used to determine how often recombination happens b/w the marker and gene
estimate of distance
how much recombination frequency is the theoretical maximum
50%
what is chance offspring will have parental type
50%
what is chance offspring will have nonparental type
50%
genes far apart on the same chromosome will exhibit how much recombination
50%
if there is 50% recombination is there linkage
no
if two markers are close together what happens to probability that there will be recombination
less chance of recombination
if two markers are close together what happens to probability that there will be recombination
less chance of recombination
what is genetic distance
estimate of physical distance measured by frequency of recombination b/w two loci
what is physical distance
the actual distance b/w two loci measured in basepairs
what happens to loci that are tightly linked
they will most likely stay together through multiple generations
there is an average of how many recombinations on homologous chromosmes in humans
2
1cM = how many base pair?
1.1 million basepair
is recombination random?
no it is non-random, different chromosomes have recombination at different frequencies
describe the diffrence b/w female and male recombination rate
females have higher recombinatino rate and so have larger genetic maps
males and females have different genetic maps, why?
females have higher recombination rate
are genetic maps in line with physical map?
no, just rough estimate of each other
why is there more recomination in females?
b/c females oocytes arrest in prophase 1 (which is where recombination happens) for years
what is minimum number of samples needed for dominant disease
10
what is minimum number of samples needed for recessive disease
20
are larger or smaller families more informative
larger
In the positional cloning workflow, what steps are taken care of b/c of genome project
second and third steps: obtaining clones of all DNA in region & identifying all the genes in the region
what do we still have to do in positional cloning workflow
still have to define candidate region, prioritize them for mutation screening, test candidate genes for mutations n affected people
What does DSH stand for?
Dyschromatosis Symmetrica Hereditaria
What is MOI of DSH
AD
how do we assess how reliable our linkage calculations are
use lod score
what does lod stand for
log of the odds
what does a lod score compare
the probabliity of obtaining our data if the 2 loci are linked at theta value versus the probablitiy that they are not linked
theta value tells you waht
distance
lod value tells you what
how reliable the distance is from theta value
if Z > 0 (positive) what does that mean
evidence for linkage
If Z < 0 (negative number) what does that mean
evidence against lnkage
What does it mean if Z > (or equal to) 3
statistically reliable evidence for linkage
what p value does Z>3 mean
p value = .05
If Z < -2 what does that mean
statistically reliable evidence against linkage
what p value does Z < -2 mean
p value = .05
if Z is b/w -2 and 3 what does that mean
evidence is inconvlusive
what is the actual theta value when looking at a graph
pick the peak of the curve
.1 theta is how many cM
10
when analyzig statistically reliable Z scores, which one is closest to disease gene
the one with smallest theta value
what is used to narrow down linkage analysis
haplotype analysis
In the DSH disease where was the mutation they found (what gene?)
DSRAD gene
function of protein can be looked at by doing what
sequencing among evolution - so seeing if sequence of gene that makes protein is conserved throughout different species
what types of mutations are causing DSH
null - loss of function
If DSH has loss of function leading to disease what is causing it
haploinsufficiency
if a chromosomal translcoation disrupts a gene it results in what
same phenotype as point mutation
can you see breakpoint karyotype
yes you can see but can’t identify where it is
what method woudl you use to identify where breakpoint is
FISH
when you see homozygosity coming from same ancestral origin what is it
autozygosity
In autozygosity mapping if it is black what does it mean
homozygosity for the snps
what is exome sequecing
method for specifcially the coding regions of all genes
what allows identification of disease genes when linkage isn’t present
exome sequencing
symptoms: distinctive faces, cardiac & skeeltal abonomalities, immunological problems, mental retardation, is what disease
kabuki syndrome
what disease was found using exome sequencing
kabuki syndrome
they think that kabuki syndrome is AD, what would cause it to be dominant
haploinsufficiency
