Abstract
Thirty-three kilobase pairs (kb) of human DNA containing the haptoglobin (Hp) and haptoglobin-related (Hpr) gene pair were cloned, and the nucleotide sequence of 21-kb DNA was determined. The two genes are closely linked, with Hpr being 2.2 kb downstream of Hp. Six hundred nucleotides of DNA occur between the two genes that are not found either 5' to the Hp gene or 3' to the Hpr gene. After the duplication event, the first intron of the Hpr gene acquired a 9-kb insert consisting mainly of a retrovirus-like element with a potential primer-binding site homologous to a mouse isoleucine tRNA. The element forms a repeated family in the human genome that I name RTVL-I (retrovirus-like element-isoleucine). In the coding region of the Hpr gene, there are no frameshift or nonsense mutations and its exon-intron splicing sites, 5' flanking and 3' flanking sequences do not show any obvious defects. There are 28 amino acid differences between the decoded amino acid sequences of the Hpr and Hp genes. Sixteen of these differences occur in the hpr beta chain, and all appear to be located on the surface of the molecule in places not thought to be involved in the hemoglobin binding function of haptoglobin. The structure of the Hpr gene suggests that the gene may be expressed and give rise to a functional product.
Highlights
Thirty-three kilobase pairs of human DNAcontaining the haptoglobin (Hp)and haptoglobin-related (Hpr)gene pair were cloned, and the nucleotide sequence of 21-kb DNA was determined
The structure of the Hpr gene suggests that the gene may be expressed and give rise to a functional product
The best characterized sequences are those homologous to theMoloney murine leukemia virus; they have a primer-binding site sequence complementary to glutamic acid tRNA (Steele et al, 1984). Another family of retrovirus-like sequences has recently been found in the human genome by Mager and Henthorn (1984)
Summary
H p gene (5' H p ; positions 778-967). Sequence matches are shown by uertical lines. Boundary of the duplicated region forming the two genes a t positions 8,821 for Hp and at 19,006 for Hpr and the. 5' boundary at 868 for Hp and at421 for Hpr.The joining region contains a 600-bp sequence not homologous to either the 3' Hpr or the 5' Hp. 7-bp direct repeats, AACACCA, flanking the 600-bp sequence are indicated with both ouer- and underlines.
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