| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q23.2 | [White blood cell count QTL] | 611862 | Autosomal recessive | 3 | ACKR1 | 613665 |
A number sign (#) is used with this entry because white blood cell count as a quantitative trait is associated with a single-nucleotide polymorphism in the ACKR1 gene (613665), which encodes the Duffy blood group antigen.
Peripheral white blood cell count (WBC) is a clinical measurement, used to determine evidence of acute inflammation or infection. In addition to elevation or depression of white blood cell levels with clinical disorders, peripheral WBC is known to vary among different racial and ethnic groups. Specifically, WBC is lower among African Americans than among European Americans (Bain et al., 1984; Reed and Diehl, 1991). Using admixture mapping, Nalls et al. (2008) analyzed data from African American participants in 2 population studies. Participants of both studies were genotyped across more than 1,322 SNPs that were preselected to be informative for African versus European ancestry and span the entire genome. Nalls et al. (2008) used these markers to estimate genetic ancestry in each chromosomal region and then tested the association between WBC and genetic ancestry at each locus. They found a locus on chromosome 1q strongly associated with WBC (p less than 10(-12)). The strongest association was with a single-nucleotide polymorphism (SNP) in the ACKR1 gene, rs2814778, a marker known to eliminate expression of the Duffy blood group antigen (see 613665.0002). Participants who had both copies of the common West African allele had a mean WBC of 4.9 (standard deviation 1.3); participants who had both common European alleles had a mean WBC of 7.1 (standard deviation 1.3). This variant explained approximately 20% of population variation in WBC.
By quadrupling the sample size from the Nalls et al. (2008) study, Reich et al. (2009) showed that low WBC in African Americans, which they referred to as benign ethnic neutropenia, primarily results from reduced neutrophil count due to homozygosity for the Duffy-null SNP, rs2814778, rather than to ancestry alone. Reich et al. (2009) noted the clinical significance of the lower neutrophil counts in individuals homozygous for the Duffy-null variant in medical decision making, as WBC is a marker of immunocompetence, infection, and inflammation, and they proposed the potential utility of rs2814778 genotyping.
Bain, B., Seed, M., Godsland, I. Normal values for peripheral blood white cell counts in women of four different ethnic origins. J. Clin. Path. 37: 188-193, 1984. [PubMed: 6693578] [Full Text: https://doi.org/10.1136/jcp.37.2.188]
Nalls, M. A., Wilson, J. G., Patterson, N. J., Tandon, A., Zmuda, J. M., Huntsman, S., Garcia, M., Hu, D., Li, R., Beamer, B. A., Patel, K. V., Akylbekova, E. L., Files, J. C., Hardy, C. L., Buxbaum, S. G., Taylor, H. A., Reich, D., Harris, T. B., Ziv, E. Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies. Am. J. Hum. Genet. 82: 81-87, 2008. Note: Erratum: Am. J. Hum. Genet. 82: 532 only, 2008. [PubMed: 18179887] [Full Text: https://doi.org/10.1016/j.ajhg.2007.09.003]
Reed, W. W., Diehl, L. F. Leukopenia, neutropenia, and reduced hemoglobin levels in healthy American blacks. Arch. Intern. Med. 151: 501-505, 1991. [PubMed: 2001132]
Reich, D., Nalls, M. A., Kao, W. H. L., Akylbekova, E. L., Tandon, A., Patterson, N., Mullikin, J., Hsueh, W.-C., Cheng, C.-Y., Coresh, J., Boerwinkle, E., Li, M., and 12 others. Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet. 5: e1000360, 2009. Note: Electronic Article. [PubMed: 19180233] [Full Text: https://doi.org/10.1371/journal.pgen.1000360]