NM_002299.2(LCT):c.-13907C>T AND Lactase persistence

Clinical significance:association (Last evaluated: Nov 20, 2018)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000008124.3

Allele description [Variation Report for NM_002299.2(LCT):c.-13907C>T]

NM_002299.2(LCT):c.-13907C>T

Genes:
LCT:lactase [Gene - OMIM - HGNC]
MCM6:minichromosome maintenance complex component 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q21.3
Genomic location:
Preferred name:
NM_002299.2(LCT):c.-13907C>T
Other names:
-13910C*T; MCM6:c.1917+326C>T
HGVS:
  • NC_000002.12:g.135851076G>A
  • NG_008104.2:g.9094C>T
  • NG_008958.1:g.30366C>T
  • NM_002299.3:c.-13907C>T
  • NM_005915.5:c.1917+326C>T
  • LRG_338t1:c.-13907C>T
  • LRG_338:g.9094C>T
  • NC_000002.11:g.136608646G>A
  • NM_002299.2:c.-13907C>T
Nucleotide change:
IVS13, C/T
Links:
OMIM: 601806.0001; dbSNP: rs4988235
NCBI 1000 Genomes Browser:
rs4988235
Molecular consequence:
  • NM_005915.5:c.1917+326C>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Lactase persistence
Identifiers:
MedGen: C1857231

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000028329OMIMno assertion criteria providedassociation
(Nov 20, 2018)
germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

Bersaglieri, T., Sabeti, P. C., Patterson, N., Vanderploeg, T., Schaffner, S. F., Drake, J. A., Rhodes, M., Reich, D. E., Hirschhorn, J. N. Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 74: 1111-1120, 2004.

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element.

Olds LC, Sibley E.

Hum Mol Genet. 2003 Sep 15;12(18):2333-40. Epub 2003 Jul 22.

PubMed [citation]
PMID:
12915462

The T allele of a single-nucleotide polymorphism 13.9 kb upstream of the lactase gene (LCT) (C-13.9kbT) does not predict or cause the lactase-persistence phenotype in Africans.

Mulcare CA, Weale ME, Jones AL, Connell B, Zeitlyn D, Tarekegn A, Swallow DM, Bradman N, Thomas MG.

Am J Hum Genet. 2004 Jun;74(6):1102-10. Epub 2004 Apr 20.

PubMed [citation]
PMID:
15106124
PMCID:
PMC1182074
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000028329.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In an analysis of a 47-kb region on chromosome 2q21 associated with hypolactasia (223100), Enattah et al. (2002) identified a variant in intron 13 of the MCM6 gene, which they designated C/T(-13910) (rs4988235), that was completely associated with the trait in Finnish families and in 3 other populations. The C/T(-13910) variant occurs approximately 14 kb upstream of the LCT gene (603202) and affects a binding site of transcription factor AP-2 (see 107580). The C allele, associated with lactase nonpersistence, is in the consensus binding motif, whereas the T variant disrupts this motif. It is possible that the AP-2 element has a long-range cis-transcriptional effect on developmental stage-specific regulation of LCT.

Olds and Sibley (2003) characterized the functional role of the C/T(-13910) polymorphism in regulating lactase gene transcription by transfecting human intestinal cells with variant/promoter-reporter constructs and assaying them for promoter activity. A 200-bp region surrounding the -13910C variant, associated with lactase nonpersistence, resulted in a 2.2-fold increase in lactase promoter activity. The -13910T variant, associated with lactase persistence, resulted in an even greater increase. The DNA sequence of the C/T(-13910) variants differentially interacted with intestinal cell nuclear proteins. The authors concluded that the DNA region of the C/T(-13910) lactase persistence/nonpersistence variant functions in vitro as a cis element capable of enhancing differential transcriptional activation of the lactase promoter.

The lactase-persistence phenotype, which is frequent in populations of northern European extraction, is found at low frequency in most populations in sub-Saharan Africa but, in some populations, particularly pastoral groups, it is significantly more frequent. Mulcare et al. (2004) tested the C-13.9kbT single-nucleotide polymorphism (SNP) in 1,671 individuals from 20 distinct cultural groups in 7 African countries. It was possible to match 7 of the groups tested with groups from the literature for whom phenotypic information was available. In 5 of these groups, the published frequencies of lactase persistence were 25% or more. However, they found the T allele to be so rare that it cannot explain the frequency of the lactase-persistence phenotype throughout Africa. They concluded that the C-13.9kbT polymorphism is not a predictor of lactase persistence in sub-Saharan Africans.

Bersaglieri et al. (2004) found that the -22018A (601806.0002) and -13910T alleles of the SNPs identified by Enattah et al. (2002) uniquely mark a lactase persistence-associated haplotype that extends over more then 800 kb in approximately 77% of European Americans studied.

Campbell et al. (2005) studied a European American panel discordant for height (see 606255), a heritable trait that varies widely across Europe. Genotyping 178 SNPs and applying standard analytical methods yielded no evidence of stratification. However, they found that the -13910C-T polymorphism (which they designated LCT -13910C-T) was strongly associated with height (P less than 10(-6)). The T allele was strongly associated with tall stature. This apparent association was largely or completely due to stratification; rematching individuals on the basis of European ancestry greatly reduced the apparent association, and no association was observed in Polish or Scandinavian individuals. Campbell et al. (2005) concluded that the failure of standard methods to detect this stratification indicates that new methods may be required.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

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