Detection of a major gene for heterocellular hereditary persistence of fetal hemoglobin after accounting for genetic modifiers

Journal Article · Tue Feb 01 04:00:00 EST 1994 · American Journal of Human Genetics; (United States)

OSTI ID:7200589

Thein, S L; Weatherall, D J ^[1]; Sampietro, M; Rohde, K; Rochette, J; Lathrop, G M; Demenais, F

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1. Institute of Molecular Medicine, Oxford (United Kingdom)

[open quotes]Heterocellular hereditary persistence of fetal hemoglobin[close quotes] (HPFH) is the term used to describe the genetically determined persistence of fetal hemoglobin (Hb F) production into adult life, in the absence of any related hematological disorder. Whereas some forms are caused by mutations in the [beta]-globin gene cluster on chromosome 11, others segregate independently. While the latter are of particular interest with respect to the regulation of globin gene switching, it has not been possible to determine their chromosomal location, mainly because their mode of inheritance is not clear, but also because several other factors are known to modify Hb F production. The authors have examined a large Asian Indian pedigree which includes individuals with heterocellular HPFH associated with [beta]-thalassemia and/or [alpha]-thalassemia. Segregation analysis was conducted on the HPFH trait FC, defined to be the percentage of Hb F-containing cells (F-cells), using the class D regressive model. The results provide evidence for the presence of a major gene, dominant or codominant, which controls the FC values with residual familial correlations. The major gene was detected when the effects of genetic modifiers, notably [beta]-thalassemia and the XmnI-[sup G][gamma] polymorphism, are accounted for in this analysis. Linkage with the [beta]-globin gene cluster is excluded. The transmission of the FC values in this pedigree is informative enough to allow detection of linkage with an appropriate marker(s). The analytical approach outlined in this study, using simple regression to allow for genetic modifiers and thus allowing the mode of inheritance of a trait to be dissected out, may be useful as a model for segregation and linkage analyses of other complex phenotypes. 39 refs., 4 figs., 6 tabs.

• OSTI ID: 7200589
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 54:2; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
CARBOXYLIC ACIDS
DETECTION
DISEASES
GENE MUTATIONS
GENES
GENETIC MAPPING
GLOBINS
HEMOGLOBIN
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
MAPPING
MATHEMATICS
METABOLIC DISEASES
MUTATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIGMENTS
PORPHYRINS
PROTEINS
REGRESSION ANALYSIS
STATISTICS