Evidence map›Paper›PMID 24959916›Full record

ArticlePloS one2014

Differences in meiotic recombination rates in childhood acute lymphoblastic leukemia at an MHC class II hotspot close to disease associated haplotypes.

Pamela Thompson, Kevin Urayama, Jie Zheng, Peng Yang, Matt Ford, Patricia Buffler, Anand Chokkalingam, Tracy Lightfoot, Malcolm Taylor

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 7 institutions in 4 countries.

Pamela ThompsonPaediatric & Familial Cancer Research Group, Institute of Cancer Sciences, University of Manchester, St Mary's Hospital, Manchester, United Kingdom.
Kevin UrayamaSchool of Public Health, University of California, Berkeley, Berkeley, California, United States of America; Department of Human Genetics and Disease Diversity, Tokyo Medical and Dental University, Tokyo, Japan.
Jie ZhengSchool of Computer Engineering, Nanyang Technological University, Singapore; Genome Institute of Singapore, A*STAR (Agency for Science, Technology, and Research), Biopolis, Singapore.
Peng YangData Analytics Department, Institute for Infocomm Research, A*STAR, Singapore.
Matt FordResearch Computing Services, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.
Patricia BufflerSchool of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
Anand ChokkalingamSchool of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
Tracy LightfootUniversity of York, Heslington, York, United Kingdom.
Malcolm TaylorIndependent Researcher, Handforth, Cheshire, United Kingdom.
University of California, Berkeley · USCheshire West and Chester · GBGenome Institute of Singapore · SGInstitute for Infocomm Research · SGSt Mary's Hospital · GBUniversity of Manchester · GBUniversity of York · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Childhood Acute Lymphoblastic Leukemia (ALL) is a malignant lymphoid disease of which B-cell precursor- (BCP) and T-cell- (T) ALL are subtypes. The role of alleles encoded by major histocompatibility loci (MHC) have been examined in a number of previous studies and results indicating weak, multi-allele associations between the HLA-DPB1 locus and BCP-ALL suggested a role for immunosusceptibility and possibly infection. Two independent SNP association studies of ALL identified loci approximately 37 kb from one another and flanking a strong meiotic recombination hotspot (DNA3), adjacent to HLA-DOA and centromeric of HLA-DPB1. To determine the relationship between this observation and HLA-DPB1 associations, we constructed high density SNP haplotypes of the 316 kb region from HLA-DMB to COL11A2 in childhood ALL and controls using a UK GWAS data subset and the software PHASE. Of four haplotype blocks identified, predicted haplotypes in Block 1 (centromeric of DNA3) differed significantly between BCP-ALL and controls (P = 0.002) and in Block 4 (including HLA-DPB1) between T-ALL and controls (P = 0.049). Of specific common (>5%) haplotypes in Block 1, two were less frequent in BCP-ALL, and in Block 4 a single haplotype was more frequent in T-ALL, compared to controls. Unexpectedly, we also observed apparent differences in ancestral meiotic recombination rates at DNA3, with BCP-ALL showing increased and T-ALL decreased levels compared to controls. In silico analysis using LDsplit sotware indicated that recombination rates at DNA3 are influenced by flanking loci, including SNPs identified in childhood ALL association studies. The observed differences in rates of meiotic recombination at this hotspot, and potentially others, may be a characteristic of childhood leukemia and contribute to disease susceptibility, alternatively they may reflect interactions between ALL-associated haplotypes in this region.

Indexed as

Genetic Predisposition to DiseaseHaplotypesRecombination, GeneticAllelesCase-Control StudiesChildChild, PreschoolCollagen Type XIFemaleGene FrequencyGenetic LociHistocompatibility Antigens Class IIHLA-D AntigensHumansMaleMeiosisCOL11A2 protein, humanCollagen Type XIHistocompatibility Antigens Class IIHLA-D AntigensHLA-DM antigens

Identifiers

PMID24959916
PMCPMC4069019
OpenAlexW2111643736

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.