Etohc1 QTL Detail

Summary

• Symbol
  Etohc1
• Name
  ethanol consumption 1
• Synonyms
  Etp1

• Feature Type
  QTL
• IDs
  MGI:1858387
  NCBI Gene: 112101
• Candidate Genes
  2 Genes

Location &
Maps

• Sequence Map
  Chr2:38129725-38129871 bp

  From MGI annotation of GRCm39
  

• View this region in JBrowse
  

• Genome Browsers
  Ensembl | UCSC | NCBI

• Genetic Map
  Chromosome 2, 24.26 cM (cM position of peak correlated region/marker)
• Mapping Data
  4 experiments

Mutations,
Alleles, and
Phenotypes

• Phenotype Summary
  1 phenotype from 2 alleles in 1 genetic background
  1 phenotype reference
  

• All Mutations and Alleles
  2
• QTL
  2
• Find Mice (IMSR)
  0 strains or lines available

Sequences &
Gene Models

• NCBI Gene
  112101

References

• Summaries
  All 6

  Phenotypes 1
• Earliest
  J:40854 Belknap JK, et al., Short-term selective breeding as a tool for QTL mapping: ethanol preference drinking in mice. Behav Genet. 1997 Jan;27(1):55-66
• Latest
  J:110030 Saba L, et al., Candidate genes and their regulatory elements: alcohol preference and tolerance. Mamm Genome. 2006 Jun;17(6):669-88

Candidate Genes for Etohc1:

Gene	Genome Location (GRCm39)	Reference	QTL Note
Kif5c	Chr2:49509310-49664790 (+)	J:110030	Candidate genes for alcohol traits were identified using gene expression analysis. Total brain RNA from 70-90 day old male mice were hybridized to DNA microarrays to detect expression differences between high and low alcohol preference selection lines (HAP and LAP, respectively) and high and low tolerance selection lines (HAFT and LAFT, respectively). All selection lines were derived from HS/Ibg and were between 19 to 24 generations of selective breeding. Candidate genes mapping to previously identified expression and behavior QTL intervals are described below. Candidate genes were also confirmed using strain distribution patterns from 30 BXD (C=C57BL/6J; D=DBA/2J) recombinant inbred (RI) strains. Kif5c (32.5 cM) on mouse Chromosome 2 exhibits differential expression between high and low acute functional tolerance strains in the BXD RI set. This gene maps near previously identified alcohol preference QTLs Alcp1 (47.5 cM), Ap2q (34 cM), Etohc1 (28 cM), Etohc2 (50 cM), and Alpq2 (45 cM). Gstm1 (108.39 Mb) on mouse Chromosome 3 is more highly expressed in high alcohol preferring lines compared to low alcohol preferring lines. D3Ertd254e (aka LOC241944) at 19 cM exhibits differential expression between high and low acute functional tolerance strains in theBXD RI set. This gene maps near a previously identified locus at D3Pas1 (22.7 cM) associated with basal cAMP signaling. Gnb1 at 79.4 cM (153.38 Mb) on mouse Chromosome 4 is more highly expressed in low alcohol preference lines compared to high alcohol preference lines (LOD=17.13). This gene maps near previously identified alcohol preference QTL Ap3q at 81 cM. Evi5 (56 cM ) and Pdap1 on mouse Chromosome 5 exhibits differential expression between high and low acute functional tolerance strains in the BXDRI set. These genes map near a locus at D5Mit201 (44 cM) suggestively linked to alcohol preference. On mouse Chromosome 9, 4930422I07Rik (88.99 Mb), D930028F11Rik (expressed sequence C130036J11; 48.5 Mb), and Mthfs (130.69 Mb) are more highly expressedin high alcohol preference lines compared to low alcohol preference lines (LOD=7.46, 9.5, and 7.16, respectively). Hyou1 (44.48 Mb) is more highly expressed in low alcohol preference lines compared to high alcohol preference lines (LOD=4.18). Hyou1 and D930028F11Rik map to the Alpq3 (alcohol preference QTL 3) interval (17 cM - 53 cM). Flnb on mouse Chromosome 14 exhibits differential expression between high and low acute functional tolerance strains in the BXD RI set. This gene maps near a previously identified QTL at D14Byu1 (o.5 cM) associated with basal and forskolin-induced cAMP signaling. Brd2 at 18.5 cM (31.81 Mb) on mouse Chromosome 17 is more highly expressed in high alcohol preferring lines compared to low alcohol preferring lines (LOD=3.93). Galnt1 (24.43 Mb) on mouse Chromosome 18 is more highly expressed in high alcohol preference lines compared to low alcohol preference lines (LOD=2.93). Tbl1x (30.9 cM) on mouse Chromosome X exhibits differential expression between high and low acute functional tolerance strains in the BXD RI set.
Stxbp1	Chr2:32677619-32737249 (-)	J:99482	Several alcohol preference QTL map to proximal mouse Chromosome 2 including Alcp1 (47.5 cM), Ap2q (34 cM), Etohc1 (28 cM), and Etohc2 (50 cM). This study investigates Stxbp1 as a candidate gene for the chromosome 2 alcohol-associated locus. Alcohol preferring inbred strain C57BL/6J and alcohol avoiding inbred strain DBA/2J differ at nucleotide 646 of the Stxbp1 sequence. G646A is a non-conservative change in the Stxbp1 coding sequence resulting in the absence of a turn/turn motif in the C57BL/6J allele. Analysis of 23 BXD RI strains shows correlation of the Stxbp1 polymorphism to alcohol consumption, acute alcohol withdrawal severity, and alcohol-induced conditioned taste aversion. This observation was confirmed in 3 other experiments. 1) Stxbp1 genotype was established for 86 (C57BL/6J x DBA/2J)F2 animals. F2 homozygotes for C57BL/6J-derived Stxbp1 alleles display 2X increased alcohol consumption compared to heterozygotes, and 3.5X increased alcohol consumption compared to F2 DBA/2J homozygotes (P=0.001).The effect of the C57BL/6J-derived Stxbp1 allele appears to be additive. 2) Fourth generation phenotype-selection lines derived from C57BL/6J and DBA/2J progenitors were assessed for allele frequencies at Stxbp1. The low alcohol preferring selection line STDRLO showed significant enrichment for DBA/2J-derived Stxbp1 alleles compared to the high alcohol preferring selection line STDRHI (P<0.0001). 3) Stxbp1 genotype and alcohol consumption was analyzed in 15 inbred strains. Ten inbred strains carrying C57BL/6J-like Stxbp1 allele tend to consume more alcohol compared to the five inbred strains carrying DBA/2J-like Stxbp1 alleles. The difference in alcohol consumption did not reach statistical significant but supports the hypothesis that Stxbp1 is a candidate gene for alcohol preference traits.