High recombination between two physically close human basement membrane collagen genes at the distal end of chromosome 13q.

Bowcock, Anne M.; Hebert, Joan M.; Wijsman, Ellen M.; Gadi, Inder K.; Cavalli-Sforza, Luca; Boyd, Charles D.

doi:10.1073/pnas.85.8.2701

Cited by 19 publications

(10 citation statements)

References 18 publications

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“…The presence of recombination hot spots in various regions of the human genome indicates a preference for crossing over to take place at discreet sites (Lebo et al 1983;Chakravarti et al 1984Chakravarti et al , 1986Rouyer et al 1986;Bowcock et al 1988;Grimm et al 1989;Charmley et al 1990;Benger et al 1991;Oudet et al 1992;Pentao et al 1992;Hubert et al 1994;Cullen et al 1995Cullen et al , 1997Reiter et al 1996;Jeffreys et al 1998;Lopes et al 1998;Smith et al 1998;Yip et al 1999;Badge et al 2000;Jeffreys et al 2000Jeffreys et al , 2001Schneider et al 2002). To identify potential hot spots for recombination over the entire MHC, 48 polymorphic markers distributed across the MHC were used to fine map the 325 MHC recombinants identified among the 12 donors studied.…”

Section: Identification Of Recombination Hot Spots Across the Mhcmentioning

confidence: 99%

“…A number of molecular genetic mechanisms, including mutation, meiotic recombination (gene conversion and crossing over), selection, and demographic history, are likely to dictate the length of haplotypic blocks and the extent of linkage disequilibrium (LD) within each block. Analyses of recombination hot spots have been reported for a number of genomic regions in humans (Lebo et al 1983;Chakravarti et al 1984Chakravarti et al , 1986Rouyer et al 1986;Bowcock et al 1988;Grimm et al 1989;Charmley et al 1990;Benger et al 1991;Oudet et al 1992;Pentao et al 1992;Hubert et al 1994;Reiter et al 1996;Jeffreys et al 1998;Lopes et al 1998;Smith et al 1998;Yip et al 1999;Badge et al 2000;Schneider et al 2002), the most detailed of which have involved the major histocompatibility complex (MHC) class II region (Cullen et al 1995(Cullen et al , 1997Jeffreys et al 2000Jeffreys et al , 2001. Recent data have indicated a convincing inverse correlation between rate of meiotic recombination and strength of LD within a 200-kb segment of the MHC class II region (Jeffreys et al 2001), providing concrete evidence that recombination plays a primary role in defining the boundaries of strongly associated haplotypic blocks.…”

Section: Introductionmentioning

confidence: 99%

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High-Resolution Patterns of Meiotic Recombination across the Human Major Histocompatibility Complex

Cullen

Perfetto

Klitz

et al. 2002

The American Journal of Human Genetics

198

210

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Definitive characteristics of meiotic recombination events over large (i.e., >1 Mb) segments of the human genome remain obscure, yet they are essential for establishing the haplotypic structure of the genome and for efficient mapping of complex traits. We present a high-resolution map of recombination at the kilobase level across a 3.3-Mb interval encompassing the major histocompatibility complex (MHC). Genotyping of 20,031 single sperm from 12 individuals resulted in the identification and fine mapping of 325 recombinant chromosomes within genomic intervals as small as 7 kb. Several principal characteristics of recombination in this region were observed: (1) rates of recombination can differ significantly between individuals; (2) intense hot spots of recombination occur at least every 0.8 Mb but are not necessarily evenly spaced; (3) distribution in the location of recombination events can differ significantly among individuals; (4) between hot spots, low levels of recombination occur fairly evenly across 100-kb segments, suggesting the presence of warm spots of recombination; and (5) specific sequence motifs associate significantly with recombination distribution. These data provide a plausible model for recombination patterns of the human genome overall.

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Section: Identification Of Recombination Hot Spots Across the Mhcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High-Resolution Patterns of Meiotic Recombination across the Human Major Histocompatibility Complex

Cullen

Perfetto

Klitz

et al. 2002

The American Journal of Human Genetics

198

210

View full text Add to dashboard Cite

show abstract

“…In the case of collagen IV, composed of two al(IV) and a2(IV) chains, the human genes have been mapped to the same segment of chromosomes 13q (3,4). More recently, the al(IV) and a2(IV) genes were determined to be separated by <650 kilobases (kb) by pulse-field electrophoresis (5).…”

mentioning

confidence: 99%

Alpha 1(IV) and alpha 2(IV) collagen genes are regulated by a bidirectional promoter and a shared enhancer.

Burbelo

Martin²,

Yamada³

1988

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

128

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Collagen IV is the major structural component of basement membranes and is a heterotrimer composed of two al(IV) and one a2(IV) chains. Most collagen genes are dispersed in the human genome, such as the genes for collagen I, which are located on chromosomes 7 [al(I)] and 17 [a2(I)].In contrast, we have found that the murine al(IV) and a2(IV) collagen chain genes exist in a head-to-head arrangement on opposite strands separated by 130 base pairs. By transfecting various portions of these genes into cells, we have found that transcription of the al(IV) and t2(IV) genes is regulated by a bidirectional promoter located between the two genes working in concert with an enhancer located in the frst intron of the al(IV) chain gene.The collagen family is composed of >20 distinct gene products coding for a variety ofhomotrimeric and heterotrimeric proteins (1). Most of the collagen genes are dispersed throughout the genome with the exception of the collagen IV and collagen VI genes (2). In the case of collagen IV, composed of two al(IV) and a2(IV) chains, the human genes have been mapped to the same segment of chromosomes 13q (3, 4). More recently, the al(IV) and a2(IV) genes were determined to be separated by <650 kilobases (kb) by pulse-field electrophoresis (5).Collagen IV, found exclusively in basement membranes, is synthesized by a variety of cultured cells, including epithelial, endothelial, muscle, and certain tumor cells (6). F9 teratocarcinoma cells provide a unique system for studying the coordinate gene regulation of the al(IV) and a2(IV) chain genes.Undifferentiated F9 teratocarcinoma cells produce very low amounts of mRNA for the al(IV) and a2(IV) chains but are rapidly induced to synthesize these mRNAs in large amounts by treatment with retinoic acid and dibutyryl cAMP (7). We have begun to identify cis-acting elements necessary for celland tissue-specific expression of the al(IV) chain gene and found that the promoter for this gene requires an enhancer located in the first intron for effective transcription (8). This sequence in the first intron was defined as an enhancer based on its ability to stimulate transcription, independent of orientation and distance. Here we report that the a2(IV) collagen gene is located 130 base pairs (bp) away in a head-to-head orientation with the al(IV) chain gene. We also show that the al(IV) and a2(IV) chain genes share a bidirectional promoter that utilizes the same enhancer within the first intron of the al(IV) collagen gene for efficient transcriptional activity. This unique gene organization and sharing of regulatory elements may be important in the coordinate expression of these genes during differentiation and development.EXPERIMENTAL PROCEDURES constructed from the promoterless pSVOCAT-X plasmid (8).The structure of the 0.78-kb promoter-CAT construct for the al(IV) (p47A) containing nucleotides 939-163 has been described (8). p47B contains nucleotides 163-939 in the opposite orientation of p47A. The DNA fragment in p47B includes 5' flanking DNA, first exon an...

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“…23 However, the chance of segregating together is not 100% because of the "phenomenon" (process) of recombination (crossing over). [252][253][254][255][256] During recombination, the naturally occurring exchange of chromosome regions between ho-mologous pairs of chromosomes happens during meiosis. 257 The chance for a recombination event to occur depends on the distance between the 2 genes on the same chromosome.…”

Section: Gene Mappingmentioning

confidence: 99%

Primer on Medical Genomics Part II: Background Principles and Methods in Molecular Genetics

Tefferi

Wieben²,

Dewald

et al. 2002

Mayo Clinic Proceedings

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High recombination between two physically close human basement membrane collagen genes at the distal end of chromosome 13q.

Abstract: GeneticsHigh recombination between two physically close human basement membrane collagen genes at the distal end of chromosome 13q (DNA

Cited by 19 publications

References 18 publications

High-Resolution Patterns of Meiotic Recombination across the Human Major Histocompatibility Complex

High-Resolution Patterns of Meiotic Recombination across the Human Major Histocompatibility Complex

Alpha 1(IV) and alpha 2(IV) collagen genes are regulated by a bidirectional promoter and a shared enhancer.

Primer on Medical Genomics Part II: Background Principles and Methods in Molecular Genetics

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