Using loss of heterozygosity data in affected pedigree member linkage tests. 1995

E d Lustbader, and T R Rebbeck, and K H Buetow
Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 19111, USA.

Linkage analysis can be used to test the hypothesis that a marker locus of known location segregates independently from a presumed disease gene. One way to test this hypothesis is to measure the similarity of marker alleles among pairs of relatives affected with the disease. When the disease under consideration is cancer, it is possible to take advantage of the marker alleles in tumors to revise the similarity measure obtained from the observations made in constitutional tissue. Only cancers that arise through the model of recessive oncogenesis are amenable to this revised analysis. This model postulates that cancer is caused by somatic genetic changes which result in the loss of one or both copies of a normal allele at a tumor suppressor locus. If an individual's inherited genotype is heterozygous at the marker locus, the model of recessive oncogenesis suggests that we may observe loss of constitutional heterozygosity at the marker locus in the tumor. In this report, we how how to incorporate this loss of heterozygosity data into affected pedigree member linkage tests. The revised procedure is illustrated using data obtained from relatives with breast cancer. Substantial improvement in the power to reject the different chromosome hypothesis is obtained when loss of heterozygosity is observed in multiple relatives with the same marker alleles retained in the tumors.

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
D009857 Oncogenes Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene. Transforming Genes,Oncogene,Transforming Gene,Gene, Transforming,Genes, Transforming
D010063 Ovum A mature haploid female germ cell extruded from the OVARY at OVULATION. Egg,Egg, Unfertilized,Ova,Eggs, Unfertilized,Unfertilized Egg,Unfertilized Eggs
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
D005260 Female Females
D005808 Genes, Recessive Genes that influence the PHENOTYPE only in the homozygous state. Conditions, Recessive Genetic,Genetic Conditions, Recessive,Recessive Genetic Conditions,Condition, Recessive Genetic,Gene, Recessive,Genetic Condition, Recessive,Recessive Gene,Recessive Genes,Recessive Genetic Condition
D005819 Genetic Markers A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. Chromosome Markers,DNA Markers,Markers, DNA,Markers, Genetic,Genetic Marker,Marker, Genetic,Chromosome Marker,DNA Marker,Marker, Chromosome,Marker, DNA,Markers, Chromosome
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006580 Genetic Carrier Screening Identification of individuals who are heterozygous at a GENETIC LOCUS for a recessive PHENOTYPE. Carriers, Genetic, Detection,Genetic Carriers, Detection,Heterozygote Detection,Carrier Detection, Genetic,Detection, Genetic Carrier,Genetic Carrier Detection,Heterozygote Screening,Carrier Screening, Genetic,Detection, Heterozygote,Screening, Genetic Carrier,Screening, Heterozygote,Screenings, Genetic Carrier

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