Name
Title | ||
|---|---|---|
Inverse inbreeding coefficient problems with an application to linkage analysis of recessive diseases in inbred populations |
Abstract | ||
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This paper addresses a family tree construction problem that arises in mapping genes that cause genetic diseases inherited in an autosomal recessive pattern. The mapping of disease-causing genes in the human genome is often carried out starting with the following major steps: (i) find related persons affected with the same disease, (ii) connect the affected relatives into one or more family pedigrees, (iii) find the genotypes of affected and unaffected relatives at a large number of variable DNA markers that span the genome, and (iv) use a collection of statistical and algorithmic tools called genetic linkage analysis to find those DNA markers that segregate with the disease. Inbred populations are used in many human genetics studies partly because the inbreeding allows rare genetic diseases to appear. Existing linkage analysis software tools are not well suited to large inbred pedigrees, so users take a variety of shortcuts either in the pedigree construction or in the linkage analysis. We formulate and investigate mathematical and algorithmic questions underlying a pedigree construction shortcut taken by Chang et al. [l]. They replaced the input pedigree by another pedigree in which the inbreeding coeficients of the affected sibships remained approximately the same where the inbreeding coefficient of a person, is the prior probability that the person inherited the same piece of DNA on both copies of the chromosome from a single ancestor. Here “prior” means depending only on the pedigree structure and not any DNA or phenotype information [2]. For example, the inbreeding coefficient of the child X of a half-sibling marriage is l/8 because the probability that the parents of X get the same allele from their common parent is l/2 and the probability that X inherits the same allele from his father [mother] is 1/2[1/2]. The replacement pedigree must include the affected sibships and their parents, and may replace the rest of the pedigree by fictitious persons and fictitious parent/child relationships. The fictitious persons typically replace real persons whose DNA is unavailable, serving only as placeholders to approximate the overall inbreeding coefficient for the affected persons. Mathematically, inbreeding coefficients can be characterized as follows: |
Year | DOI | Venue |
|---|---|---|
2000 | 10.1016/S0166-218X(00)00193-1 | Symposium on Discrete Algorithms |
Keywords | Field | DocType |
pedigree,cycles,linkage analysis,graphs,inbreeding coefficient,recessive diseases,autosomal recessive,genetic linkage,linkage,cycle,graph representation,genetics,graph theory | Population,Coefficient of relationship,Combinatorics,Demography,Inbreeding,Pedigree chart,Genetic linkage,Disease gene identification,Prior probability,Dominance (genetics),Evolutionary biology,Mathematics | Journal |
Volume | Issue | ISSN |
104 | 1 | Discrete Applied Mathematics |
ISBN | Citations | PageRank |
0-89871-434-6 | 0 | 0.34 |
References | Authors | |
1 | 3 | |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Richa Agarwala | 1 | 310 | 58.02 |
| Leslie G. Biesecker | 2 | 19 | 2.44 |
| Alejandro A. Schäffer | 3 | 827 | 136.66 |