Hemoglobin Parchman: Double Crossover Within a Single Human Gene

Adams, Joel C.; Morrison, W T; Steinberg, Martin H.

doi:10.1126/science.7123235

Cited by 43 publications

(10 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, we detected recurrent conversions between the human β- and δ-globin genes. Evidence for a similar but presumably much more recent event has been reported in a patient exhibiting mild microcytosis, whose δ-globin gene contained part of the amino acid sequence of the β-globin gene [37]. The authors of that report hypothesized that this could have been due to a new gene conversion.…”

Section: Resultsmentioning

confidence: 58%

Conversion events in gene clusters

et al. 2011

View full text Add to dashboard Cite

BackgroundGene clusters containing multiple similar genomic regions in close proximity are of great interest for biomedical studies because of their associations with inherited diseases. However, such regions are difficult to analyze due to their structural complexity and their complicated evolutionary histories, reflecting a variety of large-scale mutational events. In particular, conversion events can mislead inferences about the relationships among these regions, as traced by traditional methods such as construction of phylogenetic trees or multi-species alignments.ResultsTo correct the distorted information generated by such methods, we have developed an automated pipeline called CHAP (Cluster History Analysis Package) for detecting conversion events. We used this pipeline to analyze the conversion events that affected two well-studied gene clusters (α-globin and β-globin) and three gene clusters for which comparative sequence data were generated from seven primate species: CCL (chemokine ligand), IFN (interferon), and CYP2abf (part of cytochrome P450 family 2). CHAP is freely available at http://www.bx.psu.edu/miller_lab.ConclusionsThese studies reveal the value of characterizing conversion events in the context of studying gene clusters in complex genomes.

show abstract

Section: Resultsmentioning

confidence: 58%

Conversion events in gene clusters

et al. 2011

View full text Add to dashboard Cite

show abstract

“…One consequence of such a double cross-over would be the production of a chromosome lacking a but expressing an a-6-a gene, an event consistent with the inheritance of the Dantu antigen in cells of this type (Contreras et al, 1984). An analogous hybrid (haemoglobin Parchman) has recently been described between 6and ,?-haemo-globins (Adams et al, 1982). One prediction of this hypothesis would be the existence of Dantu-positive (a-6-a) molecules carrying an M antigen that would be Pronase-resistant on intact erythrocytes.…”

Section: Discussionmentioning

confidence: 99%

The use of monoclonal antibodies to quantify the levels of sialoglycoproteins α and δ and variant sialoglycoproteins in human erythrocyte membranes

Merry¹,

Hodson²,

Thomson³

et al. 1986

Biochemical Journal

View full text Add to dashboard Cite

By using radioiodinated monoclonal antibodies we have estimated that there are about 600 000 copies of sialoglycoprotein alpha (synonym glycophorin A) and 80 000 copies of sialoglycoprotein delta (synonym glycophorin B) per normal human erythrocyte. Erythrocytes expressing the product of only one alpha gene contain about 300 000 copies of alpha/cell. Two erythrocyte types containing alpha-delta hybrid molecules were studied. Those with heterozygous expression of the (alpha-delta)Mi.V gene contain about 100 000 alpha-delta copies per cell, whereas those with heterozygous expression of the En(UK) gene contain about 80 000 alpha-delta copies/cell. Erythrocyte types containing delta-alpha hybrid molecules were also studied. About 200 000 copies of (delta-alpha)Dantu were measured in cells with heterozygous expression of the (delta-alpha)Dantu gene (donor M.P.), whereas about 315 000 copies of the putative (delta-alpha)Dantu hybrid were found on the erythrocytes of donor J.O. [which also have heterozygous expression of the putative (delta-alpha)Dantu gene]. The erythrocytes of donor M.P. have normal levels of alpha, whereas those of donor J.O. have only about half-normal levels. It is proposed that the hybrid sialoglycoprotein of donor J.O. is of alpha-delta-alpha composition [(alpha-delta-alpha)Dantu] rather than delta-alpha and results from a double cross-over analogous to that which gives rise to haemoglobin Parchman.

show abstract

“…In addition, Hb Parchman (Adams et al 1982) seems to be another example of δ-globin gene conversion by the β-gene. Adams et al (1982) have shown that the mutated δ-globin chain has two variant amino-acids (δ22 Ala→Glu and δ50 Ser→Thr), which are the same as the β-globin "wild-type" chain. Although these data have been interpreted as a double crossover event, a con-120 (Beldjord et al 1992), the 3' boundary of the conversion, in the case of Hb F-Charlotte, might be located at position +1507, reducing the length of the converted fragment to 333 bp d The Gγ-Atlanta HPFH is a characteristic example of a "patchy" conversion event e The origin of the Cretan type of the non-deletional HPFH mutation by two different gene conversion events is unique in the human globin gene region Fig.…”

Section: Figmentioning

confidence: 99%

Contribution of gene conversion in the evolution of the human ?-like globin gene family

Papadakis¹,

Patrinos²

1999

Human Genetics

View full text Add to dashboard Cite

Gene conversion is referred to as one of two types of mechanisms known to act on gene families, mainly to maintain their sequence homogeneity or, in certain cases, to produce sequence diversity. The concept of gene conversion was established 20 years ago by researchers working with fungi. A few years later, gene conversion was also observed in the human genome, i.e. the gamma-globin locus. The aim of this article is to emphasize the role of genetic recombination, particularly of gene conversion, in the evolution of the human beta-like globin genes and further to summarize its contribution to the convergent evolution of the fetal globin genes. Finally, this article attempts to re-examine the origin and spread of specific mutations of the beta-globin cluster, such as the sickle cell or beta-thalassemia mutations, on the basis of repeated gene conversion events.

show abstract

Hemoglobin Parchman: Double Crossover Within a Single Human Gene

Cited by 43 publications

References 15 publications

Conversion events in gene clusters

Conversion events in gene clusters

The use of monoclonal antibodies to quantify the levels of sialoglycoproteins α and δ and variant sialoglycoproteins in human erythrocyte membranes

Contribution of gene conversion in the evolution of the human ?-like globin gene family

Contact Info

Product

Resources

About