Family Genetics And Inbreeding Flashcards
Inbreeding basics
Genetics about relatedness; but in the end all pedigrees join i.e. we are all relatives. Can see over several generations in many human families; individuals are inbred; they share ancestors in
common. We can extrapolate to calculate the Most Recent Common Ancestor (MRCA).
Inbreeding is the mating of relatives. If an individual is homozygous by virtue of receiving two copies of the allele from the same ancestor, the alleles show Identity by descent (IBD). In the pedigree these matings appear as ‘loops’.
Spanish Royal Family; Going back 7 generations, Aflonso XII King of Spain should have had 128 ancestors, instead had 8! Tutankhamun was a result of a brother/sister
Inbreeding and identity by descent
The more IBD the more homozygosity; i.e. inbreeding leads to loss of heterozygosity; in a
population, the variation becomes subdivided into distinct inbred lines rather than being scattered through the population as a whole. In self-fertilising plants, can be extreme. Imagine a selfing plant, heterozygous for Aa.
Proportion of homozygous increasing
Aa
AA Aa aa
AA AA Aa aa aa
AA AA AA Aa aa aa aa
In this example proportions of homozygous increases each generation, i.e., the proportion of
heterozygotes reduces each generation, and the variation is partitioned into a series of AA and aa
pure lines (although the frequencies of the A and a alleles do not change)
Human extreme mating
In humans, the most extreme is brother sister mating.
Imagine a locus with 4 alleles. Each of their parents is a heterozygote for both alleles. What is the chance of their child being a homozygote for two copies of the same allele through the fact of common descent? (Check pedigree in booklet)
There is a chance that the offspring will receive A1 by the ordinary processes of heredity. There is an additional chance of a second copy being inherited that comes from the fact that the other parent is a sib.
If, for example, he had come from far away he might have had alleles A17 and A94 and there is
no increased chance of homozygosity. But, since he is a brother, there is an increased chance of
identity by descent; taken into account by adding the second pathway through which the A1 allele
can reach the child. The chance that the offspring will be homozygous by descent alone is ½ x ½ = ¼.
Measuring F - the coefficient of inbreeding
F - the probability that a pair of alleles at a locus will be identical by descent. Every inbred pedigree has a loop in it that links the two mates through their shared ancestors
F= ∑ N (1/2)n, where N is the number of loops and n is the number of ancestors in each loop; from the child (not counted) to its parents, and back to the shared ancestor, and back down to the other parent. Thus, for brother-sister mating:
F = 2 x (1/2)^3 = 2 x 1/8 = 1/4
For cousin mating, it is 2 x (1/2)5 = 1/16. As degree of kinship decreases, the value of F decreases rapidly. However, F can build up over the generations (which is why we have the “sum of” the number of loops in the formula).
Check pedigree in booklet
Each pathway in the loop goes through 5 ancestors, back to the grandfather and grandmother respectively. F = 2 x (1/2)5 = 1/16 for cousin marriages – a common mating type.
Inbreeding depression
Inbreeding is associated with a decrease in fitness called inbreeding depression.
This is caused the increase in homozygosity of rare deleterious alleles
Inbreeding and pedigree dogs
Many pedigree dogs suffer from inbreeding depression (reduction in fitness associated with
inbreeding) e.g. The inbreeding coefficient for Border Collies has increased with time and led to
diseases such as Congenital myopathy (wasting of the muscles).
Syringomelia in the King Charles spaniel which are selected for flat faces. Bulldogs have changed in phenotype over time.
Inbreeding and animals
Long-term monitoring studies in song sparrows showed that the immune response (determined
using a scratch test) decreased with inbreeding. All white tigers are descended from a single
individuals caught in India called Mohan; today there are many programmes in zoo to promote
outbreeding.
Inbreeing in humans examples
All populations in the end inbred, but some much more so than others - e.g. if one lives on a small
island or tiny village, there is little option but to mate with someone who shares a recent ancestor with you.
Can lead to local patches of high frequency of recessive disease - e.g. Finland which has 33
unique genetic diseases such as Variant Late Infantile neuronal ceroid lipofuscinoses VLINCL, which traces back to a single male in a pedigree.
Rates of inbreeding can be approximated using the diversity of surnames in a population. London
has a greater diversity in surnames than say Wales.
Runs of homozygosity
continuous lengths of homozygous genotypes that are present in an individual due to parents passing on identical haplotypes to their offspring.
Runs of homozygosity are more common in people living on islands of Croatia than the mainland Croatia.
Similar results comparing islands in Scotland and the mainland. Having more runs of homozygosity are associated with human diseases such as colon cance
