Optimal ascertainment strategies to detect linkage to common disease alleles. 1998

J A Badner, and E S Gershon, and L R Goldin
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, MD 20892-1274, USA. jbadner@helix.nih.gov

Traditionally, extended pedigrees with many affected individuals have been studied for the purpose of detection of linkage. For traits caused by a rare susceptibility allele, this is a productive strategy. However, this sampling strategy may not work well for traits determined by multiple loci in which one or more have common susceptibility alleles. We simulated three single-additive-locus models of inheritance and two-locus models with additive or multiplicative interactions, all with rare or common susceptibility alleles. A trait locus was linked, with no recombination, to a marker locus with four equally frequent alleles. Family structure varied, but the total number of affected individuals was held constant. Two generations of individuals were genotyped. We used three nonparametric affected-sib-pair programs and two nonparametric pedigree-analysis programs to perform linkage analysis. For single-locus, additive, and multiplicative models, we found that, when the susceptibility allele was rare, (frequency .0025), extended pedigrees with first or second cousins had the most power for detection of linkage. However, when the susceptibility allele was common in the single-locus, additive, and multiplicative two-locus models (frequency .25), extended pedigrees were no more powerful than nuclear families. There was also a decrease in power when the pedigrees had a greater number of affected individuals, more so for the single-locus and multiplicative models than for the additive model. We conclude that for single-locus, additive, and multiplicative models of qualitative traits with common alleles, there is no benefit to the collection of extended pedigrees, and there may be a loss of power in the collection of pedigrees with many affected individuals.

UI MeSH Term Description Entries
D008040 Genetic Linkage The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME. Genetic Linkage Analysis,Linkage, Genetic,Analyses, Genetic Linkage,Analysis, Genetic Linkage,Genetic Linkage Analyses,Linkage Analyses, Genetic,Linkage Analysis, Genetic
D008297 Male Males
D008957 Models, Genetic Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Genetic Models,Genetic Model,Model, Genetic
D009679 Nuclear Family A family composed of spouses and their children. Daughters,Sons,Daughter,Families, Nuclear,Family, Nuclear,Nuclear Families,Son
D010375 Pedigree The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition. Family Tree,Genealogical Tree,Genealogic Tree,Genetic Identity,Identity, Genetic,Family Trees,Genealogic Trees,Genealogical Trees,Genetic Identities,Identities, Genetic,Tree, Family,Tree, Genealogic,Tree, Genealogical,Trees, Family,Trees, Genealogic,Trees, Genealogical
D002874 Chromosome Mapping Any method used for determining the location of and relative distances between genes on a chromosome. Gene Mapping,Linkage Mapping,Genome Mapping,Chromosome Mappings,Gene Mappings,Genome Mappings,Linkage Mappings,Mapping, Chromosome,Mapping, Gene,Mapping, Genome,Mapping, Linkage,Mappings, Chromosome,Mappings, Gene,Mappings, Genome,Mappings, Linkage
D004198 Disease Susceptibility A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. Diathesis,Susceptibility, Disease,Diatheses,Disease Susceptibilities,Susceptibilities, Disease
D005190 Family A social group consisting of parents or parent substitutes and children. Family Life Cycles,Family Members,Family Life Cycle,Family Research,Filiation,Kinship Networks,Relatives,Families,Family Member,Kinship Network,Life Cycle, Family,Life Cycles, Family,Network, Kinship,Networks, Kinship,Research, Family
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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