Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
10577928
TITLE
An optimal algorithm for automatic genotype elimination.
ABSTRACT
In an effort to accelerate likelihood computations on pedigrees, Lange and Goradia defined a genotype-elimination algorithm that aims to identify those genotypes that need not be considered during the likelihood computation. For pedigrees without loops, they showed that their algorithm was optimal, in the sense that it identified all genotypes that lead to a Mendelian inconsistency. Their algorithm, however, is not optimal for pedigrees with loops, which continue to pose daunting computational challenges. We present here a simple extension of the Lange-Goradia algorithm that we prove is optimal on pedigrees with loops, and we give examples of how our new algorithm can be used to detect genotyping errors. We also introduce a more efficient and faster algorithm for carrying out the fundamental step in the Lange-Goradia algorithm-namely, genotype elimination within a nuclear family. Finally, we improve a common algorithm for computing the likelihood of a pedigree with multiple loops. This algorithm breaks each loop by duplicating a person in that loop and then carrying out a separate likelihood calculation for each vector of possible genotypes of the loop breakers. This algorithm, however, does unnecessary computations when the loop-breaker vector is inconsistent. In this paper we present a new recursive loop breaker-elimination algorithm that solves this problem and illustrate its effectiveness on a pedigree with six loops.
DATE PUBLISHED
1999 Dec
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 1999/12/01 09:00
medline 2000/03/21 09:00
entrez 1999/12/01 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
O'Connell JR O'Connell J R JR University of Pittsburgh, Department of Human Genetics, Pittsburgh, PA 15261, USA. jeff@watson.hgen.pitt.edu.
Weeks DE Weeks D E DE
INVESTIGATORS
JOURNAL
VOLUME: 65
ISSUE: 6
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 1999
MONTH: Dec
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0002-9297
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
AG16992-01 NIA NIH HHS United States
HG00932 NHGRI NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Algorithms
Alleles
Female
Genotype
Humans
Likelihood Functions
Male
Nuclear Family
Pedigree
Research Design
Software
Time Factors
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's