Fine mapping of polymorphic alcohol-related quantitative trait loci candidate genes using interval-specific congenic recombinant mice.
- Authors
- Ehringer, Marissa A; Thompson, Jessica; Conroy, Otakuye; Yang, Fan; Hink, Raquel; Bennett, Beth; Johnson, Thomas E; Sikela, James M
- Year
- 2002
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 12436047
- DOI
- 10.1097/01.ALC.0000036921.33411.67
BACKGROUND: The inbred long-sleep (ILS) and inbred short-sleep (ISS) strains of mice are widely studied as a model of initial sensitivity to alcohol. Recently, a large comparative DNA sequencing study of candidate genes located within the four Lore quantitative trait loci (QTLs) associated with the ethanol-induced loss of righting reflex in ILS and ISS mice has identified eight genes that contain coding region differences corresponding to amino acid changes. Here, recently developed interval-specific congenic recombinant mice (ISCRs) have been used to map these genes in relationship to newly narrowed QTL regions. METHODS: Regions of candidate genes containing DNA differences corresponding to previously identified amino acid changes between ISS and ILS mice were amplified from either genomic DNA or complementary DNA from ISCR mice using polymerase chain reaction. The products were purified and directly sequenced to determine the genotypes for each polymorphism. On the basis of these genotypic data, each candidate gene was determined to be located either within or outside of recently narrowed Lore QTL intervals. RESULTS: Of these eight candidates with protein-coding differences, five are now excluded from their respective Lore intervals. The other three (Znf142, Ptprn, and Znf133) have been localized to the narrowed QTL intervals. CONCLUSIONS: These three central nervous system genes (Znf142, Ptprn, and Znf133) represent promising candidates for involvement in the differential sensitivity to alcohol exhibited between ILS and ISS mice. This study also demonstrates how the combination of high-throughput comparative gene sequencing and concomitant genetic fine mapping of QTL regions with ISCRs can be an effective tool for accelerating the process of moving from QTL to gene.
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| A Critical Review of Methods and Results in the Search for Genetic Contributors to Alcohol Sensitivity. | 2018 | 29623680 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| A Critical Review of Methods and Results in the Search for Genetic Contributors to Alcohol Sensitivity. | Schuckit MA | — | 2018 | → |
| Exome sequencing and arrayCGH detection of gene sequence and copy number variation between ILS and ISS mouse strains. | Dumas L et al. | — | 2014 | → |
| A quantitative trait locus on chromosome 18 is a critical determinant of excitotoxic cell death susceptibility. | Lorenzana A et al. | — | 2007 | → |
| Alcohol dependence is associated with the ZNF699 gene, a human locus related to Drosophila hangover, in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) sample. | Riley BP et al. | — | 2006 | → |
| DNA microarray and proteomic strategies for understanding alcohol action. | Sikela JM et al. | — | 2006 | → |
| Expression profiling identifies novel candidate genes for ethanol sensitivity QTLs. | MacLaren EJ et al. | — | 2006 | → |
| Identification of susceptibility loci for alcohol-related traits in the Irish Affected Sib Pair Study of Alcohol Dependence. | Kuo PH et al. | — | 2006 | → |
| Cerebellar gene expression profiling and eQTL analysis in inbred mouse strains selected for ethanol sensitivity. | MacLaren EJ et al. | — | 2005 | → |
| Quantitative trait loci mapping for ethanol sensitivity and neurotensin receptor density in an F2 intercross derived from inbred high and low alcohol sensitivity selectively bred rat lines. | Radcliffe RA et al. | — | 2004 | → |