Complete sequence and structure of the gene for human adenosine deaminase

Abstract

The nucleotide sequence of the human adenosine deaminase gene was determined. The gene was isolated in a series of overlapping lambda phage clones containing human germ line DNA. A total of 36,741 base pairs were sequenced, including 32,040 base pairs from the transcription initiation site to the polyadenylation site, 3935 base pairs of 5'-flanking DNA, and 766 base pairs of 3'-flanking DNA. The gene contains 12 exons separated by 11 introns. The exons range in size from 62 to 325 base pairs while the introns are 76-15 166 base pairs in size. The area sequenced contains 23 copies of Alu repetitive DNA and a single copy of an "O" family repeat. All but one of these repeat sequences are located in the first three introns or the 5'-flanking region. The apparent promoter region of the gene lacks the "TATA" and "CAAT" sequences often found in eucaryotic promoters and is extremely G/C rich. Contained within this region are areas homologous to other G/C-rich promoters, including six decanucleotide sequences that are highly homologous to sequences identified as functional binding sites for transcription factor Sp1.

Mutations in the human adenosine deaminase gene that affect protein structure and RNA splicing.

“…These additional 5' sequences agree with genomic sequence of this region (24,25) and indicate that there are multiple transcription initiation sites within the 5' end of the human ADA gene. S1 nuclease analysis of the 5' ends of ADA mRNA in our laboratory (J.C.S., unpublished data) has shown that there is a major initiation site, base 1 of the consensus sequence, and several very minor initiation sites.…”

“…We have previously reported a similar ADA cDNA sequence pADA3-3 (21). In both cases, the intron 7 sequence is identical to intron 7 of the normal ADA gene (24,25 we do not believe that the absence of exon 7 or the inclusion of intron 7 is relevant to ADA deficiency.…”

“…The paired amino acids are derived from the codon sequence of the consensus and the codon sequence with the noted base change. Base number 1 is the first base of the major initiation start site (24 large deletions affecting intron 6, exon 7, and intron 7 in the ADA-deficient cell lines GM2756 and GM2825A. The same general strategy was used to analyze the exon 4 deletion in GM2825A.…”

Genomic organization and DNA sequences of human 17β‐hydroxysteroid dehydrogenase genes and flanking regions

“…Alu elements are distributed at random, but they have also been found to cluster within specific genomic loci (Korenberg and Rykowski, 1988;Degen and Davie, 1987;Wiginton et al, 1986). Multiple Alu sequences (17 complete and 8 partial) are also clustered in the region examined here, covering approximately 30% of the sequenced DNA.…”

Recombination mediates production of an extrachromosomal circular DNA containing a transposon-like human element, THE-1

“…A variety of characteristics including the presence of an A-rich 3' tail and variably sized target site duplications have led to the classification of Alu and L-1 sequences as retroposons. Most of the evidence supporting the mobility of these elements is based on structural and evolutionary considerations, but recent data strongly suggest that at least some members of these families are responsible for insertional (transpositional) mutagenesis (3,(16)(17)(18)(19)(20). The presence of LTRs and uniformly sized short direct repeats has led to the assignment of THE-1 as a proretroviral-like transposable element (1,2).…”