Year-end Sale % OFF 
Abstract
Alcohol dependence is a typical example of a complex trait that is governed by several genes and for which the mode of inheritance is unknown. We analyzed the microsatellite markers and the Affymetrix single-nucleotide polymorphisms (SNPs) for a subset of the Collaborative Study on the Genetics of Alcoholism family sample, 93 pedigrees of Caucasian ancestry comprising 919 persons, 390 of whom are affected according to DSM III-R and Feighner criteria. In particular, we performed parametric single-marker linkage analysis using MLINK of the LINKAGE package (for the microsatellite data), as well as multipoint MOD-score analysis with GENEHUNTER-MODSCORE (for the microsatellite and SNP data). By use of two liability classes, different penetrances were assigned to males and females. In order to investigate parent-of-origin effects, we calculated MOD scores under trait models with and without imprinting. In addition, for the microsatellite data, the MOD-score analysis was performed with sex-averaged as well as sex-specific maps. The highest linkage peaks were obtained on chromosomes 1, 2, 7, 10, 12, 13, 15, and 21. There was evidence for paternal imprinting at the loci on chromosomes 2, 10, 12, 13, 15, and 21. A tendency to maternal imprinting was observed at two loci on chromosome 7. Our findings underscore the fact that an adequate modeling of the genotype-phenotype relation is crucial for the genetic mapping of a complex trait.
Highlights
Alcohol dependence occurs in many populations; it represents a complex trait with clear familial aggregation
We focus on the microsatellite and the Affymetrix single-nucleotide polymorphism (SNP) markers typed for the Collaborative Study on the Genetics of Alcoholism (COGA) family sample [1]
The red graph shows the MOD scores obtained under four-penetrance trait models that take imprinting into account, and the blue graph shows the MOD scores obtained under the nonimprinting constraint
Summary
Alcohol dependence occurs in many populations; it represents a complex trait with clear familial aggregation. In a MOD-score analysis, the LOD score is maximized over the genetic position of the putative trait locus, and with respect to the parameters of the disease model, i.e., the penetrances and the disease allele frequency [2]. We used the program GENEHUNTER-MODSCORE [7], which maximizes the LOD score with respect to the penetrances and disease allele frequency It is a further development of our program GENEHUNTER-IMPRINTING [8] which is based on the original GENEHUNTER version 2.1 [9-11]]. When analyzing the microsatellite data, we selected the 'modcalc single' option under which a separate maximization over trait model parameters is performed for each genetic position of the putative trait locus The penetrances for both sexes were varied. Please note that coordinates from this map are different from the COGA map
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
