Identification of a novel @entity26317 gene mutated in lpd @entity19 with hypertriglyceridemia and associated with dyslipidemia in XXXX .

@entity1 @entity43227 @entity1560 @entity19 @entity72583 @entity72581 @entity26317 @entity412 @entity72580 @entity72582 @entity731 @entity165
@entity412 (TG) metabolism is crucial for whole body and local energy homeostasis and accumulating evidence suggests an independent association between plasma TG concentration and increased @entity731 risk. We previously generated a @entity19 insertional mutation lpd (lipid defect) whose phenotype included elevated plasma TG and @entity1560 . Using shotgun sequencing (approximately 500 kb) and bioinformatics, we have now identified a novel @entity26317 gene @entity72580 (lpd @entity26317 ) within the lpd locus, and demonstrate the genetic disruption of exon 10 of @entity72580 in the lpd mutant locus. @entity72580 is highly expressed in the testis and weakly expressed in the liver of 2-week old @entity19 . @entity1 @entity72580 cDNA was subsequently cloned, and was found to encode a 460AA protein with 71% protein sequence identity to @entity19 @entity72580 and approximately 35% identity to other known lipases. We next sequenced the @entity1 @entity72580 gene exons in hypertriglyceridemic subjects and normal controls, and identified seven SNPs within the gene exons and six SNPs in the adjacent introns. Two hypertriglyceridemic subjects were heterozygous for a rare DNA variant, namely @entity43227 ( @entity72581 ), which was absent from 600 normal chromosomes. Two other coding SNPs were associated with variation in plasma HDL @entity165 in independent normolipidemic populations. Using bioinformatics, we identified another novel @entity26317 designated @entity72582 (for @entity72582 ), which had 44% protein sequence identity with @entity72580 . Together with the phospholipase gene @entity72583 , @entity72582 form a new @entity26317 gene subfamily, which is characterized by shortened lid motif. Study of this @entity26317 subfamily may identify novel molecular mechanisms for plasma and/or tissue TG metabolism.
