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- Kemkemer, Claus, et al.
(author)
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Enrichment of brain-related genes on the mammalian X chromosome is ancient and predates the divergence of synapsid and sauropsid lineages
- 2009
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In: Chromosome Research. - : Springer Science and Business Media LLC. - 0967-3849 .- 1573-6849. ; 17:6, s. 811-820
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Journal article (peer-reviewed)abstract
- Previous studies have revealed an enrichment of reproduction- and brain-related genes on the human X chromosome. In the present study, we investigated the evolutionary history that underlies this functional specialization. To do so, we analyzed the orthologous building blocks of the mammalian X chromosome in the chicken genome. We used Affymetrix chicken genome microarrays to determine tissue-selective gene expression in several tissues of the chicken, including testis and brain. Subsequently, chromosomal distribution of genes with tissue-selective expression was determined. These analyzes provided several new findings. Firstly, they showed that chicken chromosomes orthologous to the mammalian X chromosome exhibited an increased concentration of genes expressed selectively in brain. More specifically, the highest concentration of brain-selectively expressed genes was found on chicken chromosome GGA12, which shows orthology to the X chromosomal regions with the highest enrichment of non-syndromic X-linked mental retardation (MRX) genes. Secondly, and in contrast to the first finding, no enrichment of testis-selective genes could be detected on these chicken chromosomes. These findings indicate that the accumulation of brain-related genes on the prospective mammalian X chromosome antedates the divergence of sauropsid and synapsid lineages 315 million years ago, whereas the accumulation of testis-related genes on the mammalian X chromosome is more recent and due to adaptational changes.
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| 2. |
- Kuhl, Angelika, et al.
(author)
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Myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 : corroboration and narrowing of the critical region on 10q22.3
- 2008
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In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 16:3, s. 367-373
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Journal article (peer-reviewed)abstract
- Several years ago, autosomal dominant myofibrillar myopathy (MFM) in combination with arrhythmogenic right ventricular cardiomyopathy (ARVC7) was tentatively mapped to a 10.6-Mbp (million base pairs) region on chromosome 10q22.3 between D10S605 (78.9 Mbp) and D10S215 (89.5 Mbp) in a Swedish family assuming that ARVC7 was allelic with cardiomyopathy, dilated 1C (CMD1C). To date, neither the genetic defect in ARVC7 nor CMD1C has been reported. In a comprehensive follow-up study were-examined and confirmed the previous linkage data for ARVC7 using a high-density single nucleotide polymorphism marker panel from Affymetrix (Human Mapping 10K Array). No other regions with significant evidence for linkage were discovered. The critical interval was narrowed down to 4.27 Mbp between D10S1645 and D10S1786. This reduced the total number of candidate genes to 18 of which 17 (RAI17, PPIF, C100RF56, SFTPA1, SFTPA2, SFTPA1B, SFTPA2B, SFTPD, C100RF57, PLAC9, ANXA11, MAT1A, DYDC1, DYDC2, C100RF58, TSPAN14 and SH2D4B) are shared with the CMD1C region. No disease-causing mutation was found in their coding regions. Moreover, metavinculin (VCL) and ZASP/cypher (LDB3) proximal and distal to this linked region were excluded by sequence analysis. To search for submicroscopic and intragenic deletions by PCR, we generated hybrid cell lines carrying only the affected or normal chromosome 10 homolog. All sequence tagged sites and exons were present on both homologs. We speculate that regulatory mutations in 1 of the 18 genes from 10q22.3 are responsible for a heterogenous spectrum of clinically distinct myodegenerative disorders, affecting both skeletal and cardiac muscles to variable degrees.
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