Mendel Complications #10

Question 1

List the factors that can cause mendelian complications

Answer 1

Age of onset, common recessive alleles, paternity exclusion, incomplete penetrance, expressivity, male lethality, de novo mutations, germ line mosaic, mitochondrial inheritance, phenocopies, complementation

Question 2

Explain common recessive alleles

Answer 2

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

Question 3

What is incomplete penetrance

Answer 3

When the person has the genotype but the trait is not completely expressed as a phenotype

Question 4

Explain expressivity

Answer 4

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

Question 5

What is male lethality

Answer 5

Is an X linked dominant disorder that is fatal for hemizygous males. It is mostly associated with IP, OFDS, and FDH

Question 6

Who or what is a sporadic case

Answer 6

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

Question 7

What is germ line mosaicism

Answer 7

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

Question 8

Explain the issue of mitochondrial inheritance

Answer 8

Mutations in the mitochondrial genome, are always passed onto the children as most of the zygotes mitochondria is maternal,

Question 9

What is heteroplasm

Answer 9

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

Question 10

Explain phenocopies

Answer 10

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

Question 11

Explain complementation

Answer 11

When 2 alleles complement each other and when they bind they form the wild type allele

Question 12

What is linkage analysis. What is it used for

Answer 12

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

Question 13

What are the rules and regulations when performing a linkage analysis

Answer 13

You must be following an unknown gene through many generations, you must find genetic markers that signify the location of said gene.

Question 14

What are the traits of a multiplex family

Answer 14

One which has many generations and many affected individuals and a clear cut phenotype

Question 15

Name 2 genetic markers

Answer 15

SNP and microsatellites

Question 16

What are haplotypes

Answer 16

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

Question 17

Linage analysis is based on?

Answer 17

the recombinants present, and genotyping the microsatellite markers

Question 18

what is the formula for theta? (recombination fraction)

Answer 18

of recombinant gametes/ #of informative meiosis

Question 19

what are the assumptions we make for a linkage analysis?

Answer 19

you must assume the nature of the disease, and that there is 100% penetrance

Question 20

what is an informative meiosis? What is non-informative meiosis

Answer 20

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

Question 21

what value of theta is desired?

Answer 21

one closest to 0, this shows that the gene we are looking for is very close to the genetic marker

Question 22

what is a LOD score?

Answer 22

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)

Question 23

what does the LOD score graph tell us?

Answer 23

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)

Question 24

who is a recombinant individual?

Answer 24

the person whose genotype is attributed a different sign than other genotypes

Question 25

what 3 things does the LOD score take into account?

Answer 25

the unknown phase, the incomplete penetrance, the possibility that some families could have a disease-gene different from other ones (locus heterogeneity)

Question 26

what are Z values?

Answer 26

multipoint linkage analysis