Clustering of pedigrees using marker allele frequencies: impact on linkage analysis.
Ethnicity may form the basis for locus heterogeneity at certain susceptibility loci for complex diseases. Classification of pedigrees into ethnic groups is usually based upon self-report, but this may not be sensitive or specific. We investigated whether it is possible to cluster families from an admixed population using pedigree-specific marker allele frequencies. We used 323 autosomal microsatellite markers from 216 pedigrees who described themselves as either Caucasian or African American. First, we compared the stated ethnicity of pedigrees with clusters using pedigree-specific marker allele frequencies as input for a self-organizing map, a type of neural network. Using data from different chromosomes, nine pedigrees which were self-reported as African American were clustered with the Caucasian pedigrees. Removal of these nine pedigrees from the African American group did not markedly affect linkage results. We then proceeded to determine whether there was further heterogeneity between pedigrees using 1 x 3 nodes. Forty-four pedigrees were clustered in a group intermediate to the African American or Caucasian clusters. This group was composed of 36 and 8 pedigrees that described themselves as African American and Caucasian, respectively. Linkage analysis was performed in this group and results compared with the groups based upon self-reported ethnicity. Linkage to a region on chromosome 3 was observed in this intermediate group, which was more significant than any of the results obtained when pedigrees were grouped using self-reported ethnicity. Use of marker data may assist in clustering pedigrees with similar, ethnic backgrounds and may increase the power for genetic linkage studies.
Grigull
J
J
Neuroscience Unit, Toronto Western Research Institute, Toronto, Ontario, Canada.
Alexandrova
R
R
Paterson
A D
AD
D000328:Adult; D000483:Alleles; D001249:Asthma / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D044383:Black People / Q000235:genetics; D002648:Child; D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D016000:Cluster Analysis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D010375:Pedigree; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
D005819:Genetic Markers