A transcribed gene in an intron of the human factor VIII gene

Levinson, Barbara; Kenwrick, Susan; Lakich, Delia; Hammonds, R. Glenn; Gitschier, Jane

doi:10.1016/0888-7543(90)90512-s

Cited by 165 publications

(92 citation statements)

References 42 publications

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“…In eukaryotes, nested genes are rare and can be located within an intron of another gene (15,16). It is noteworthy that 39 (31%) of our primate-specific TUs were nested.…”

Section: Primate-specifc Tus Are Frequently Intercalated In the Intromentioning

confidence: 99%

Global discovery of primate-specific genes in the human genome

Tay

Blythe

Lipovich

2009

Proc. Natl. Acad. Sci. U.S.A.

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The genomic basis of primate phenotypic uniqueness remains obscure, despite increasing genome and transcriptome sequence data availability. Although factors such as segmental duplications and positive selection have received much attention as potential drivers of primate phenotypes, single-copy primate-specific genes are poorly characterized. To discover such genes genomewide, we screened a catalog of 38,037 human transcriptional units (TUs), compiled from EST and cDNA sequences in conjunction with the FANTOM3 transcriptome project. We identified 131 TUs from transcribed sequences residing within primate-specific insertions in 9-species sequence alignments and outside of segmental duplications. Exons of 120 (92%) of the TUs contained interspersed repeats, indicating that repeat insertions may have contributed to primate-specific gene genesis. Fifty-nine (46%) primate-specific TUs may encode proteins. Although primate-specific TU transcript lengths were comparable to known human gene mRNA lengths overall, 92 (70%) primate-specific TUs were single-exon. Thirty-two (24%) primate-specific TUs were localized to subtelomeric and pericentromeric regions. Forty (31%) of the TUs were nested in introns of known genes, indicating that primate-specific TUs may arise within older, protein-coding regions. Primate-specific TUs were preferentially expressed in reproductive organs and tissues ( P < 0.011), consistent with the expectation that emergence of new, lineage-specific genes may accompany speciation or reproduction. Of the 33 primate-specific TUs with human Affymetrix microarray probe support, 21 were differentially expressed in human teratozoospermia. In addition to elucidating the likely functional relevance of primate-specific TUs to reproduction, we present a set of primate-specific genes for future functional studies, and we implicate nonduplicated pericentromeric and subtelomeric regions in gene genesis.

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“…In eukaryotes, nested genes are rare and can be located within an intron of another gene (15,16). It is noteworthy that 39 (31%) of our primate-specific TUs were nested.…”

Section: Primate-specifc Tus Are Frequently Intercalated In the Intromentioning

confidence: 99%

Global discovery of primate-specific genes in the human genome

Tay

Blythe

Lipovich

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…In one case, the intron 22 copy recombined with a fourth, truncated copy of int22h, to generate a smaller inversion (Naylor et al 1996). An 8-kb segment of int22h is 99.9% similar among the three copies, with a 1.8-kb intronless gene (F8A) within each of the repeat elements (Levinson et al 1990), although it is not known whether F8A is expressed during spermatogenesis.…”

Section: Wwwgenomeorgmentioning

confidence: 99%

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Ji¹,

Eichler²,

Schwartz³

et al. 2000

Genome Res.

231

158

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Chromosome-specific low-copy repeats, or duplicons, occur in multiple regions of the human genome. Homologous recombination between different duplicon copies leads to chromosomal rearrangements, such as deletions, duplications, inversions, and inverted duplications, depending on the orientation of the recombining duplicons. When such rearrangements cause dosage imbalance of a developmentally important gene(s), genetic diseases now termed genomic disorders result, at a frequency of 0.7–1/1000 births. Duplicons can have simple or very complex structures, with variation in copy number from 2 to >10 repeats, and each varying in size from a few kilobases in length to hundreds of kilobases. Analysis of the different duplicons involved in human genomic disorders identifies features that may predispose to recombination, including large size and high sequence identity between the recombining copies, putative recombination promoting features, and the presence of multiple genes/pseudogenes that may include genes expressed in germ cells. Most of the chromosome rearrangements involve duplicons near pericentromeric regions, which may relate to the propensity of such regions to accumulate duplicons. Detailed analyses of the structure, polymorphic variation, and mechanisms of recombination in genomic disorders, as well as the evolutionary origin of various duplicons will further our understanding of the structure, function, and fluidity of the human genome.

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“…The fragment was prepared from plasmid p482.6 (ATCC catalogue no. 57203) as previously described (8). Southern Wots were prehybridized and hybridized in QuilcHyb hybridization solution (Stratagene).…”

Section: Southern Blotsmentioning

confidence: 99%

“…Intron 22, the largest intron in the gene, contains two transcribed sequences, gene A (8) and gene B (9). Interestingly, gene B is transcribed in the same orientation as factor VIE and uses exons 23 to 26 of the gene (9).…”

Section: Introductionmentioning

confidence: 99%

Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells

et al. 1994

Self Cite

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The factor VIII gene, which Is defective In hemophilia A, Is located In the last megabase of the long arm of the X chromosome. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomerlc to it account for nearly half of all cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the Inversion process, and that, therefore, the event originates predominantly in male germ cells. In all 20 informative cases In which the inversion originated in a maternal grandparent, DNA polymorphism analysis determined that it occurred in the male germline. In addition, all but one of 50 mothers of sporadic cases due to an inversion were carriers. Thus, these data support the hypothesis and Indicate that factor VIII gene inversions leading to severe hemophilia A occur almost exclusively In male germ cells.

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A transcribed gene in an intron of the human factor VIII gene

Cited by 165 publications

References 42 publications

Global discovery of primate-specific genes in the human genome

Global discovery of primate-specific genes in the human genome

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells

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