Sequence variation at multiple loci influences red cell hemoglobin concentration. Blood 2010 Dec 16;116(25):e139-49
Date
09/14/2010Pubmed ID
20833975Pubmed Central ID
PMC3031420DOI
10.1182/blood-2010-05-283879Scopus ID
2-s2.0-78650486903 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
A substantial genetic contribution underlies variation in baseline peripheral blood counts. We performed quantitative trait locus/loci analyses to identify chromosome regions harboring genes influencing red cell hemoglobin concentration using the cell hemoglobin concentration mean (CHCM), a directly measured parameter analogous to the mean cell hemoglobin concentration. Fourteen significant loci (gene symbols Chcmq1-Chcmq14) were detected. Seven of these influenced CHCM in a sex-specific fashion, and 2 showed significant interactive effects (epistasis). For quantitative trait locus/loci detected in multiple crosses, confidence intervals were narrowed using statistical and bioinformatic approaches. Two strong candidate genes emerged and were further analyzed: adult β-globin (Hbb) for Chcmq3 on Chr 7, and transferrin (Trf) for Chcmq2 on Chr 9. High and low allele parental strains in crosses detecting Chcmq3 segregate 100% with the known ancestral haplotype blocks, hemoglobin (Hb) diffuse (Hbb(d)) and Hb single (Hbb(s)), respectively. Hbb(d) consists of nonidentical major and minor polypeptides and exhibits an increased positive charge relative to Hbb(s) due to the net loss of 2 negative residues in the Hbb(dminor) polypeptide, resulting in a pI of 7.85 versus 7.13. Thus, as shown in human erythrocytes, positively charged Hbs are associated with cell dehydration and increased CHCM in mouse erythrocytes.
Author List
Peters LL, Shavit JA, Lambert AJ, Tsaih SW, Li Q, Su Z, Leduc MS, Paigen B, Churchill GA, Ginsburg D, Brugnara CAuthor
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsChromosomes, Mammalian
Crosses, Genetic
Erythrocytes
Female
Genetic Variation
Haplotypes
Hemoglobins
Humans
Male
Mice
Mice, Inbred A
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred DBA
Quantitative Trait Loci
beta-Globins
