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Sequence variation at multiple loci influences red cell hemoglobin concentration.

ABSTRACT: 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 ?-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.

SUBMITTER: Peters LL

PROVIDER: S-EPMC3031420 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Sequence variation at multiple loci influences red cell hemoglobin concentration.

Peters Luanne L LL Shavit Jordan A JA Lambert Amy J AJ Tsaih Shirng-Wern SW Li Qian Q Su Zhiguang Z Leduc Magalie S MS Paigen Beverly B Churchill Gary A GA Ginsburg David D Brugnara Carlo C

Blood 20100910 25

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 ...[more]

PMID: 20833975

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Project description:Abnormally shaped red blood cells (RBCs), called poikilocytes, can cause anemia. At present, the biochemical abnormalities in poikilocytes are not well understood. Normal RBCs and poikilocytes were analyzed using whole-blood and single-cell methods. Poikilocytes were induced in rat blood by intragastrically administering titanium dioxide (TiO2) nanoparticles. Complete blood count and inductively coupled plasma mass spectrometry analyses were performed on whole-blood to measure average RBC morphology, blood hemoglobin (HGB), iron content, and other blood parameters. Follow-up confocal Raman spectroscopy was performed on single RBCs to analyze cell-type-specific HGB content. Two types of poikilocytes, acanthocytes and echinocytes, were observed in TiO2 blood samples, along with normal RBCs. Acanthocytes (diameter 7.7??±??0.5???m) and echinocytes (7.6??±??0.6???m) were microscopically larger (p??<??0.05) than normal RBCs (6.6??±??0.4???m) found in control blood samples (no TiO2 administration). Similarly, mean corpuscular volume was higher (p??<??0.05) in TiO2 whole-blood (70.70??±??1.97??fl) than in control whole-blood (67.42??±??2.03??fl). Poikilocytes also had higher HGB content. Mean corpuscular hemoglobin was higher (p??<??0.05) in TiO2 whole-blood (21.84??±??0.75??pg) than in control whole-blood (20.8??±??0.32??pg). Iron content was higher (p??<??0.001) in TiO2 whole-blood (697.0??±??24.5??mg??/??l) than in control whole-blood (503.4??±??38.5??mg??/??l), which supports elevated HGB as iron is found in HGB. HGB-associated Raman bands at 1637, 1585, and 1372??cm??-??1 had higher (p??<??0.001) amplitudes in acanthocytes and echinocytes than in RBCs from control blood and normal RBCs from TiO2 blood. Further, the 1585-cm??-??1 band had a lower (p??< ?0.05) amplitude in normal RBCs from TiO2 versus control RBCs. This represents biochemical abnormalities in normal appearing RBCs. Overall, poikilocytes, especially acanthocytes, have elevated HGB.

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Sequence variation at multiple loci influences red cell hemoglobin concentration.

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Sequence variation at multiple loci influences red cell hemoglobin concentration.

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