ABSTRACT
The HTR1A -1019C>G genotype was associated with major depression in the Utah population. Linkage analysis on Utah pedigrees with strong family histories of major depression including only cases with the HTR1A -1019G allele revealed a linkage peak on chromosome 10 (maximum HLOD=4.4). Sequencing of all known genes in the linkage region revealed disease-segregating single-nucleotide polymorphisms (SNPs) in LHPP. LHPP SNPs were also associated with major depression in both Utah and Ashkenazi populations. Consistent with the linkage evidence, LHPP associations depended on HTR1A genotype. Lhpp or a product of a collinear brain-specific transcript, therefore, may interact with Htr1a in the pathogenesis of major depression.
Subject(s)
Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/genetics , Genetic Linkage , Inorganic Pyrophosphatase/genetics , Receptor, Serotonin, 5-HT1A/genetics , Chromosomes, Human, Pair 10 , Female , Genotype , Humans , Jews/genetics , Jews/statistics & numerical data , Male , Pedigree , Polymorphism, Single Nucleotide , Risk Factors , Utah/epidemiologyABSTRACT
Potassium channels govern the permeability of cells to potassium ions, thereby controlling the membrane potential. In metazoa, potassium channels are encoded by a large, diverse gene family. Previous analyses of this gene family have focused on its diversity in mammals. Here we have pursued a more comprehensive study in Caenorhabditis elegans, Drosophila melanogaster, and mammalian genomes. The investigation revealed 164 potassium channel encoding genes in C. elegans, D. melanogaster, and mammals, classified into seven conserved families, which we applied to phylogenetic analysis. The trees are discussed in relation to the assignment of orthologous relationships between genes and vertebrate genome duplication.
