Mendel Complications #10 Flashcards
List the factors that can cause mendelian complications
Age of onset, common recessive alleles, paternity exclusion, incomplete penetrance, expressivity, male lethality, de novo mutations, germ line mosaic, mitochondrial inheritance, phenocopies, complementation
Explain common recessive alleles
These recessive alleles can cause autosomal recessive disorders, two people from the same isolated population can be heterozygous and have the recessive gene for the same disorder and thus once mated could have an affected child
What is incomplete penetrance
When the person has the genotype but the trait is not completely expressed as a phenotype
Explain expressivity
Two people may have the same genotype yet ones phenotype could be more severe than the others. This is does to environmental factors and the presence of modifier genes
What is male lethality
Is an X linked dominant disorder that is fatal for hemizygous males. It is mostly associated with IP, OFDS, and FDH
Who or what is a sporadic case
When an individual has a disorder with no trace of the same disorder in their family history, this is due to a de novo mutation
What is germ line mosaicism
It can affect both the germ line and somatic cells, a wild type individual can have the germ line mutation and pass it onto its progeny
Explain the issue of mitochondrial inheritance
Mutations in the mitochondrial genome, are always passed onto the children as most of the zygotes mitochondria is maternal,
What is heteroplasm
Is when there is more than one type of mutation in the mitochondrial maternal DNA. Therefore severity of the disease depends on percentage of affected mitochondria split between the daughter cells
Explain phenocopies
Is when there is a disease with an associated genotype and another illness that has the same phenotype as this disease but no associated genotype
Explain complementation
When 2 alleles complement each other and when they bind they form the wild type allele
What is linkage analysis. What is it used for
Is an approach based on an analysis of pedigrees and recombinant and nonrecombinant individuals. It is used to locate the location of the gene causing a disorder
What are the rules and regulations when performing a linkage analysis
You must be following an unknown gene through many generations, you must find genetic markers that signify the location of said gene.
What are the traits of a multiplex family
One which has many generations and many affected individuals and a clear cut phenotype
Name 2 genetic markers
SNP and microsatellites
What are haplotypes
They are a group of alleles that are on the same chromosome, the closer they are ( theta is less than 50%) the more likely they are to travel together. Note that you end up with more parental than recombinant strands
Linage analysis is based on?
the recombinants present, and genotyping the microsatellite markers
what is the formula for theta? (recombination fraction)
of recombinant gametes/ #of informative meiosis
what are the assumptions we make for a linkage analysis?
you must assume the nature of the disease, and that there is 100% penetrance
what is an informative meiosis? What is non-informative meiosis
an informative meiosis takes place when we know the definite genotypes of the parents of the generation, a non-informative one is when we dont know the history/genotypes of the parent because we do not have their parents’ genotypes
what value of theta is desired?
one closest to 0, this shows that the gene we are looking for is very close to the genetic marker
what is a LOD score?
it is the probability fraction (in words)= P that the 2 loci are in linkage / P that the 2 loci are not in linkage.
(in math) log10= L(theta<0.5)/L(theta=0.5)
what does the LOD score graph tell us?
we want a peak in the positive region this shows that the gene that is mutated in affected individuals is always near specific marker, note that the farther we get from the centromere and towards the telomere there is more -ve values showing that crossing over has occurred and thus the genes are not close to their respective markers
A LOD score above/equal to 3 is good. (mean 1:1000 chance that the gene is located near to the marker)
who is a recombinant individual?
the person whose genotype is attributed a different sign than other genotypes
what 3 things does the LOD score take into account?
the unknown phase, the incomplete penetrance, the possibility that some families could have a disease-gene different from other ones (locus heterogeneity)
what are Z values?
multipoint linkage analysis
