Lore1 QTL Detail

Summary

• Symbol
  Lore1
• Name
  loss of righting induced by ethanol 1

• Feature Type
  QTL
• IDs
  MGI:1096557
  NCBI Gene: 109471
• Candidate Genes
  5 Genes

Location &
Maps

• Sequence Map
  Chr1:75549191-92941077 bp

  From MGI annotation of GRCm39
  

• View this region in JBrowse
  

• Genome Browsers
  Ensembl | UCSC | NCBI

• Genetic Map
  Chromosome 1, 44.69 cM (cM position of peak correlated region/marker)
• Mapping Data
  9 experiments

Mutations,
Alleles, and
Phenotypes

• Phenotype Summary
  4 phenotypes from 2 alleles in 2 genetic backgrounds
  6 phenotype references
  

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

Sequences &
Gene Models

• NCBI Gene
  109471

References

• Summaries
  All 13

  Phenotypes 6
• Earliest
  J:40119 Bennett B, et al., Mapping quantitative trait loci for ethanol-induced anesthesia in LSxSS recombinant inbred and F2 mice: methodology and results. Alcohol Alcohol Suppl. 1994;2:79-86
• Latest
  J:151159 Bennett B, et al., Genetic dissection of quantitative trait locus for ethanol sensitivity in long- and short-sleep mice. Genes Brain Behav. 2008 Aug;7(6):659-68

Candidate Genes for Lore1:

Gene	Genome Location (GRCm39)	Reference	QTL Note
Htr5b	Chr1:121437571-121456194 (-)	J:93175	Potential candidate genes mapping near Lore1 on mouse Chromosome 1 are Pthr2, Ptpn4, Zfp142 (41.5 cM), and Htr5b (63 cM). Pthr2, Ptpn4, and Zfp142 have been sequenced and are polymorphic between inbred strains LS and IS.
Pth2r	Chr1:65321215-65428403 (+)	J:93175	Potential candidate genes mapping near Lore1 on mouse Chromosome 1 are Pthr2, Ptpn4, Zfp142 (41.5 cM), and Htr5b (63 cM). Pthr2, Ptpn4, and Zfp142 have been sequenced and are polymorphic between inbred strains LS and IS.
Ptpn4	Chr1:119580197-119765281 (-)	J:93175	Potential candidate genes mapping near Lore1 on mouse Chromosome 1 are Pthr2, Ptpn4, Zfp142 (41.5 cM), and Htr5b (63 cM). Pthr2, Ptpn4, and Zfp142 have been sequenced and are polymorphic between inbred strains LS and IS.
Xrcc5	Chr1:72346586-72434111 (+)	J:105312	Candidate genes for ethanol sensitivity QTL Lore1 (loss of righting induced by ethanol 1), Lore2, Lore4, and Lore5 were identified using Affymetrix gene microarray analysis. RNA from the cerebella of male animals from inbred strains LS and SS were hybridized to 2 different sets of Affymetrix gene chips and analyzed for gene expression differences. The inbred strain LS exhibits increased alcohol sensitivity compared to SS. A total of 15 candidate genes were identified, 4 of which have polymorphisms betweenLS and SS. Xrcc5 (42 cM) was identified as candidate gene for Lore1 (54 cM) on mouse Chromosome 1. Xrcc5 exhibits 2.5-fold increased expression in the SS inbred strain compared to the LS inbred strain. In addition the human ortholog XRCC5 is also associated with ethanol-induced loss of righting response. Pcsk2 (81.4 cM), Slc22a4 (28 cM), and Rassf2 were identified as candidate genes for Lore2 (85 cM) on mouse Chromosome 2. Pcsk2 and Slc22a4 exhibit 2.9-fold and 2.4-fold increased expression in LS compared to SS, respectively, whereas Rassf2 exhibits 2.4-fold increased expression in SS compared to LS. Two polymorphisms were detected in the promoter region of Slc22a4, one of which disrupts a putative SP-1 transcription factor binding site in the SS sequence. In addition, the human ortholog SLC22A4 is associated with ethanol-induced loss of righting response in humans. Six polymorphisms were detected in the Rassf2 promoter, two of which disrupt putative SP-1 transcription factor binding sites in the SS sequence. Myo1d (46 cM), BG075643 (a cDNA clone), Ebf1 (20 cM), Stx8, Tax1bp3, and Tnfaip1 (45 cM) were identified as candidate genes for Lore4 (49 cM) on mouse Chromosome 11. Myo1d and BG075643 are expressed 6.2-fold higher in LS compared to SS strains. Ebf1 is expressed 2.1-fold higher, Stx8 is expressed 2-fold higher, Tax1bp3 is expressed 2.2-fold higher, and Tnfaip1 is expressed 2-fold higher in SS compared to LS strains. The Stx8 promoter sequence has 2 polymorphisms between LS and SS, and the Tax1bp3 promoter sequence has 4 polymorphisms, one of which results in disruption of a putative NF-kB transcription factor binding site in the LS strain. Cthrc1, Krt2-8 (58.9 cM), Lgals2, Scrt1, and Atf1 were identified as candidate genes for Lore5 (46 cM) onmouse Chromosome 15. Atf1 is expressed 2-fold higher in SS compared to LS strains. Cthrc1 (3.2-fold), Krt2-8 (2.3-fold), Lga1s2 (2-fold), and Scrt1 (2.4-fold) are expressed higher in LS compared to SS strains.
Zfp142	Chr1:74605490-74627308 (-)	J:93175	Potential candidate genes mapping near Lore1 on mouse Chromosome 1 are Pthr2, Ptpn4, Zfp142 (41.5 cM), and Htr5b (63 cM). Pthr2, Ptpn4, and Zfp142 have been sequenced and are polymorphic between inbred strains LS and IS.