Exam 3 Mapping and Pedigree Flashcards
Chiasma
a point of contact between two paired chromosomes during meiosis from which crossing over and the exchange of genetic material can occur
Crossing over
The actual physical process of reciprocal exchange of chromosome segments at corresponding positions along homologous chromosomes. A process that involves symmetrical breaking and rejoining of segments.
Coupling
two wild-type alleles are on one homologous chromosome and the mutant alleles are on the other
Repulsion
each chromosome has one wild type allele and one mutant allele
Test cross
involves the breeding of a heterozygous individual with a homozygous recessive individual, in order to determine the zygosity of the former by analyzing proportions of the offspring and their phenotypes
Genetic Map
a representation of the genetic distance separating nonallelic genes in a linkage structure
Linkage analysis
Inheritance of genes is
on the same chromosome
Mendel’s Laws
1st law- segregation
2nd law-independent assortment
Mendel’s first Law
Segregation
individuals possess two alleles and a parent passes only one allele to their offspring
Mendel’s second law
independent assortment
the inheritance of one pair of genes is independent of the inheritance of the other pair
Chromosome theory of inheritance ideas
- Genes reside on chromosomes
- genes and chromosomes show parallel behavior
- Genes and chromosomes occur in pairs, 2 alleles of a gene pair are located on homologous sites on homologous chromosomes
- during meiosis due to pairing and subsequent segregation of homologous chromosomes genes also segregate
Chromosome theory of inheritance main idea
chromosomes are the carriers of genetic heredity and genes are situated on chromosomes
Genetic Linkage
when two genes are located on the same chromosome they exhibit linkage
Recombination
a process by which segments of DNA are broken and recombine to produce new combinations of alleles
Where does recombination usually take place
Anaphase 1 during meiosis
The recombination process
created genetic diversity at the level of the genes that reflects differences in the DNA sequences of different organisms
Complete linkage
when the genes are located close to one another on the same chromosomes and no recombinants are produced
Incomplete linkage
when genes are on the same chromosome but are far enough apart that some recombination occurs, but they do not assort independently
Linked genes segregate
together
In a testcross at least one heterozygous individual of the progeny are expected to
display at least one of the original parental phenotypes
In a testcross independent assortment produces what type of ratio
1:1:1:1
50% parental (non-recombinants)
50% nonparental (recombinants)
Why, when, how, and where does mitotic recombination occur
repair of breaks
interphase
different mechanisms
common fragile sites in the genome
Parental ‘Non-recombinant’ Gametes
the progeny of a cross (or genotype of the gametes) that have combinations of alleles that are like the one or the other of the parents
Non-parental ‘Recombinant’ Gametes
the progeny of a cross (or genotype of the gametes) that have non-parental combinations of alleles. These gametes result from processes of genetic recombination
If two genes are completely linked will they assort independently
No
If two genes are not linked they will assort
independently
No crossing over means
alleles of linked genes do not assort independently
genes segregate together such that gametes are the same as parents
Gene linkage is broken so recombinants are changed chromosomes
crossing over
If two genes are incompletely linked the parental gametes will be at a
higher frequency
Recombination frequency equation
of recombinant progeny over total # of progeny X 100
A coupling phase of linkage
when like alleles, dominant or recessive, are linked
Linkage types- Alleles in Coupling
recombinants- less frequently occurs- always lesser number
nonrecombinants- larger number
In Repulsion
when dissimilar alleles (e.g. dominant for one gene and recessive for the other) are linked
Outcome of independent assortment
25%
25%
25%
25%
outcome of complete linkage (coupling)
50%
50%
Linkage with crossing over (coupling)
> 50%
<50%
Goodness of fit
theoretical relation based on expected progeny ratio that when calculating degrees of freedom no parameters are estimated
Independence
based on only observed progeny ratio
a chi-squared test can be used to
determine in genes are linked
Number expected formula for testing independent assortment using chi-squared test
(row total X column total) over grand total
1% recombination equals
1 centimorgan
Genetic mapping
the process of determining the relative positions of nonallelic genes on the chromosomes of a species using genetic crosses to locate genes on chromosomes relative to one another
steps to desining a genetic map
- design crosses involving traits of interest
- observe progeny ratios
- determine whether or no the genes are linked (chi-squared test vs. expected ratio)
- determine recombination frequencies
- determine the linkage arrangement (coupling or repulsion)
- position genes on chromosomes in a way that best suits the data
When genes are linked, the parents are
always the most frequent classes while recombinants are the least frequent classes because they result from recombination
In a double cross over, progeny reflect
nonrecombinant gametes
Recombination frequency formula
sum of recombinants over sum of progeny times 100
Multiple crossovers
effect on progeny outcomes
Three point test cross
a test cross involving three linked genes in a small region of the chromosome
it is a testcross of a trihybrid
Steps to determining gene order for a 3-point cross
- identify the nonrecombinants progeny (two most numerous progeny)
- identify the double-crossover progeny (two least numerous progeny)
- compare the phenotypes of the double-crossover progeny with the phenotypes of nonrecombinant progeny. should be alike in two characteristics and different in one. the characteristic that differ between the double-crossover and the nonrecombinant progeny is encoded by the middle gene
Coefficient of coincidence
the ratio of observed double crossovers to expected double crossovers
interference
degree that one crossover interferes with other crossovers
how to calculate interference
take the percentages and multiply them
take that times the total progeny
divide the number of observed crosses by the expected double cross overs
1- the number gotten in the previous step
Genetic linkage mapping process
- find sets of related patients
- assemble patients into pedigrees
- genotype patients and other family members
- find genotypes that are inherited with the disease
- identify the region where they are located
Logarithm of odds (LOD)
estimation of the probabilities of obtaining the observed results under the assumption of linked genes with defined recombination or independent assortment. the ratio of these two probabilities is the LOD score
In general, LOD scores of 3 or higher indicate
linkage
Genome wide association
the nonrandom association between a trait and alleles at many loci throughout the genome
haplotype
a specific set of linked alleles along a chromosome
linkage disequilibrium
the nonrandom association between alleles at two or more loci in a general population
Single nucleotide polymorphism (SNP)
positions in the genome where a single nucleotide varies across individuals
GWAS Process
- goal is to identify genomic regions associated with a phenotype
- fit a statistical model at each SNP in the genome
- use fitted models to test null hypothesis: no association with SNP and phenotypes
Features of a haplotype
a haplotype is a particular pattern of sequential SNPs found on a single chromosome
Haplotype has a block-wise structure separated by recombination spots
within each block, recombination is rare due to tight linkage and only very few haplotypes
Non-variable region
area with very little variation
blank spots on chromosomes
Why is linkage disequilibrium so useful in GWAS studies
determines the extent to which association mapping can be used in species
what do linkage disequilibrium measure
the degree to which alleles at two loci are non-randomly associated
Pedigree
a pictorial diagram of the family history, that outlines the inheritance of one or more traits
Proband
first affected person that comes to the attention of the geneticist
Autosomal dominant trait facts
both sexes equally
both sexes transmit to offspring
affected individuals have an affected parent
affected parent is heterozygous, Aa, and the other parent is unaffected 1/2 of the offspring will be affected
unaffected parents don’t transmit the trait
Autosomal recessive trait facts
both sexes equally
skips generation
affected individuals born to unaffected parents
if both parents are heterozygous, Aa, then about 1/4 of the offspring will be affected
more frequent occurrence with inbreeding
On average each person is a carrier for how many recessive diseases
20
consanguineous
denoting people descending from the same ancestor
inbreeding
how are consanguineous breedings useful in genetics
help find recessive traits
IBD
identity by descent
segments are the same inherited over generations
X-linked recessive trait facts
more males than females are affected
affected sons born to unaffected mothers
half of a carrier mother’s sons are affected
never passed from father to son
all daughters of affected father are carriers
X-linked dominant trait facts
males and females are usually affected, often more females than males are affected
affected male parent passes the trait to all daughters and no sons
does not skip generations
affected mothers if heterozygous pass the trait to half the sons and half the daughters
Y-linked traits
transmitted from father to son
only males
does not skip generations
Genetic mosaicism
individuals whose cells hold different genetic constitutions- 30% of cells
Dizygotic
twins arise when two different eggs are fertilized by two different sperm
50%
Monozygotic
twins arise when one egg fertilized by one sperm splits in early development into two embryos
100%
Concordance
the percentage of twin pairs that are concordant (both twins pairs have the trait) for a trait
Why is adoption useful for studying the influence of genes and the environment?
Identical twins with the same genetics can be raised in different environments to determine what is affected by genes vs. environment
Genetic Counseling
a process of communication where patients are provided information relevant to the transmission of heritable disorders
Genetic testing methods used today
maternal blood screening
non-invasive prenatal screening
presymptomatic
pharmacogenetic
newborn
Interpreting genetic test is complicated by
the presence of multiple causative mutations, incomplete penetrance, and influence of environmental factors
Genetic information nondiscrimination act
a law that prohibits health care insurers from using genetic information in making decisions about providing health care coverage and rates