[Linkage analysis of a family with familial hypertriglyceridemia].
OBJECTIVE
To perform linkage analysis and mutation screening in a Chinese family with familial hpertriglyceridemia (FHTG).


METHODS
Thirty-two family members including 12 hypertriglyceridemia patients participated in the study. Genotyping and haplotype analysis for 22 subjects were performed using short tandem repeat (STR) microsatellite polymorphism markers on 16 candidate genes and/or loci related to lipid metabolism. Two of the sixteen known candidate genes, APOA2 and USF1 were screened for mutation by direct DNA sequencing.


RESULTS
No linkage was found between the candidate genes/loci of APOA5, LIPI, RP1, APOC2, ABC1, LMF1, APOA1-APOC3-APOA4, LPL, APOB, CETP, LCAT, LDLR, APOE and the phenotype in this family. The two-point Lod scores (theta =0) were all less than-1.0 for all the markers tested. Linkage analysis suggested linkage to chromosome 1q23.3-24.2 between the disease phenotype and STR marker D1S194 with a two-point maximum Lod score of 2.44 at theta =0. Fine mapping indicated that the disease gene was localized to a 5.87 cM interval between D1S104 and D1S196. No disease-causing mutation was detected in the APOA2 and USF1 genes.


CONCLUSIONS
The above mentioned candidate genes were excluded as the disease causing genes for this family. The results implied that there might be a novel gene/locus for FHTG on chromosome 1q23.3-1q24.2.
Tang
Xin
X
Sichuan Provincial Key Laboratory for Human Disease Gene, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan, 610072, PR China.
Lin
Ying
Y
Liu
Bing
B
Ma
Shi
S
Yang
Yang
Y
Yang
Zheng-lin
ZL
D000328:Adult; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree