Evidence map›Paper›PMID 20003225›Full record

ArticleBMC genetics2009

An experimental assessment of in silico haplotype association mapping in laboratory mice.

Sarah L Burgess-Herbert, Shirng-Wern Tsaih, Ioannis M Stylianou, Kenneth Walsh, Allison J Cox, Beverly Paigen

Abstract read
In one paragraph

Article in BMC genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. The Potential ofGenes · 2023
    Article
  2. In silico mapping of quantitative trait loci (QTL) regulating the milk ionome in mice identifies a milk iron locus on chromosome 1.Mammalian genome : official journal of the International Mammalian Genome Society · 2018
    Article
  3. In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci.Mammalian genome : official journal of the International Mammalian Genome Society · 2015
    Article
  4. Article
  5. Deconstructing Mus gemischus: advances in understanding ancestry, structure, and variation in the genome of the laboratory mouse.Mammalian genome : official journal of the International Mammalian Genome Society · 2013
    Review
  6. Article
  7. Integrative assessment of chlorine-induced acute lung injury in mice.American journal of respiratory cell and molecular biology · 2012
    Article
  8. Article
  9. Article
  10. Forward genetic approaches to understanding complex behaviors.Current topics in behavioral neurosciences · 2012
    Review
  11. Haplotype association mapping of acute lung injury in mice implicates activin a receptor, type 1.American journal of respiratory and critical care medicine · 2011
    Article
  12. Article
  13. Article
  14. Article
  15. Genome-wide association studies and genetic risk assessment of liver diseases.Nature reviews. Gastroenterology & hepatology · 2010
    Review
  16. Strain screen and haplotype association mapping of wheel running in inbred mouse strains.Journal of applied physiology (Bethesda, Md. : 1985) · 2010
    Article
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

6 authors.

Sarah L Burgess-HerbertThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
Shirng-Wern Tsaih
Ioannis M Stylianou
Kenneth Walsh
Allison J Cox
Beverly Paigen

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI Anna Karolina Palucka · 1985 to 2026
$61.9M
UNC and PERLEGEN, IncP50GM076468 · NIGMS · JACKSON LABORATORY · PI SVENSON, KAREN L · 2006 to 2015
$31.0M
From QTL to Gene for HDL CholesterolR37HL077796 · NHLBI · JACKSON LABORATORY · PI PAIGEN, BEVERLY J · 2009 to 2018
$4.3M
Cloning QTL Genes for Plasma HDL CholesterolR01HL081162 · NHLBI · JACKSON LABORATORY · PI KORSTANJE, RONNY · 2006 to 2013
$3.3M
From QTL to Gene for HDL CholesterolR01HL077796 · NHLBI · JACKSON LABORATORY · PI PAIGEN, BEVERLY J · 2004 to 2008
$2.1M
NCI NIH HHS CA34196NHLBI NIH HHS HL77796NHLBI NIH HHS HL81162NHLBI NIH HHS R01 HL081162NIGMS NIH HHS GM076468
6 · The paper itself

Abstract

backgroundTo assess the utility of haplotype association mapping (HAM) as a quantitative trait locus (QTL) discovery tool, we conducted HAM analyses for red blood cell count (RBC) and high density lipoprotein cholesterol (HDL) in mice. We then experimentally tested each HAM QTL using published crosses or new F2 intercrosses guided by the haplotype at the HAM peaks.

resultsThe HAM for RBC, using 33 classic inbred lines, revealed 8 QTLs; 2 of these were true positives as shown by published crosses. A HAM-guided (C57BL/6J x CBA/J)F2 intercross we carried out verified 2 more as true positives and 4 as false positives. The HAM for HDL, using 81 strains including recombinant inbred lines and chromosome substitution strains, detected 46 QTLs. Of these, 36 were true positives as shown by published crosses. A HAM-guided (C57BL/6J x A/J)F2 intercross that we carried out verified 2 more as true positives and 8 as false positives. By testing each HAM QTL for RBC and HDL, we demonstrated that 78% of the 54 HAM peaks were true positives and 22% were false positives. Interestingly, all false positives were in significant allelic association with one or more real QTL.

conclusionBecause type I errors (false positives) can be detected experimentally, we conclude that HAM is useful for QTL detection and narrowing. We advocate the powerful and economical combined approach demonstrated here: the use of HAM for QTL discovery, followed by mitigation of the false positive problem by testing the HAM-predicted QTLs with small HAM-guided experimental crosses.

Indexed as

Erythrocyte CountHaplotypesQuantitative Trait LociAllelesAnimalsCholesterol, HDLComputational BiologyFemaleMaleMiceMice, Inbred StrainsCholesterol, HDL

Identifiers

PMID20003225
PMCPMC2797012

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.