Fine mapping of the neurally expressed gene SOX14 to human 3q23, relative to three congenital diseases

Abstract

Members of the Sox gene family encode transcription factors that have diverse and important functions during development. We have recently described the cloning of chick and mouse Sox14 and the expression of these genes in a population of ventral interneurons in the embryonic spinal cord. We report here the cloning and sequencing of the human orthologue of Sox14. Human SOX14 shows remarkable sequence conservation compared with orthologues from other vertebrate species and probably mirrors the expression of these genes in the developing brain and spinal cord. Using radiation hybrid mapping and fluorescence in situ hybridisation, we have localised SOX14 close to the sequence tagged site D3S1576 on human chromosome 3q23. Three congenital disorders have been localised to this region: blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), Charcot-Marie-Tooth neuropathy type IIB (CMT2B) and Mobius syndrome type 2 (MBS2). We have found that SOX14 is unlikely to be involved in any of these disorders because of the position of SOX14 proximal to a BPES breakpoint and the lack of SOX14 coding region alterations in BPES, CMT2B and MBS2 patients.

Remarkable evolutionary conservation of SOX14 orthologues

“…of this group play a major role in neural development. The five intron-less group B Sox genes (Sox1, Sox2, Sox3, Sox14 and Sox21) participate in the earliest events of central nervous system (CNS) differentiation in Drosophila, Xenopus, chick and mouse (Collignon et al 1996;Uchikawa et al 1999;Hargrave et al 2000a;Kishi et al 2000;McKimmie et al 2005). Based on the sequence analysis and functional studies in vertebrates, the group B Sox genes can be further subdivided into sub-group B1 comprising activators (Sox1, Sox2 and Sox3) and sub-group B2 consisting of repressors (Sox14 and Sox21) (Uchikawa et al 1999).…”

Assignment<footref rid="foot01">¹</footref> of the mouse <i>Pcolce2</i> gene, which encodes procollagen C-proteinase enhancer protein 2, to chromosome 9 and localization of PCOLCE2 to human chromosome 3q23

“…8944) had previously been mapped, with a "minor positional discrepancy", to the interval D3S3694-D3S3546 (cM 158-160), as typed by the Stanford mapping server, and to the interval D3S3546-D3S1569 (cM 160-162), as typed by the Whitehead/MIT or Sanger Center server. All of these markers are telomeric to D3S1576 (cM 156), which maps to 3q23 (Hargrave et al, 2000), while D3S1569 has been mapped to 3q21 (r)q23 (Deloukas et al, 1998) thus localizing PCOLCE2 within 3q23. Recent deposition of a 771,896-bp contig of human chromosome 3 (working draft *sequence segment NT_005772) in the databases shows PCOLCE2 to be a 10 exon F80-kb gene that lies within the D3S546-D3S1569 interval 163.4 kb telomeric to marker D3S3546 and 121.6 kb telomeric to D3S2362.…”

Examining the genetics of congenital facial paralysis—a closer look at Moebius syndrome

“…In addition, there are numerous other developmental genes that may interact with environmental factors during the required time period of brainstem growth [8]. Table 2 lists the proposed candidate genes and their function based on previous studies in the literature [46,48,53,54,[58][59][60][61][62][63][64][65].…”

“…Its genetic locus is distal to the MBS2 locus, but promoter or enhancer elements could be mutated. However, the analysis of MBS patients does not reveal any mutations in this gene [63]. GATA-binding protein 2 (GATA2) was analyzed due to its role as a transcription factor and its expression in rhombomere 4 of the developing hindbrain and that it is regulated by HOXB1.…”