Human Molecular Genetics, 1993, Vol. 2, No. 9 1461-1462

Localization of the human TAX-1 gene to1q32.1: a region implicated inmicrocephaly and Van der WoudesyndromeSusan Kenwrick*, Margaret Leversha1, Lesley Rooke2, Thomas Hasler3 and Peter Sonderegger3

Department of Meddne, Un*vsrety of Cambridge, Addenbrooka1* Hospital, Cambridge C82 2QO, 'Department of Pathology. University of Cambridge, Cambridge,Imperial Cancer Research Fund, Claire Hal Laboratories South Mmms, Potters Bar, Hartforshlre ENG 3LD, UK and 3Bochembchee Inattut der UrtaraKat Zurich,VHrrtBrthureratrasae 190, CH-8057, Zurich, Switzerland

Received July 9, 1993; Accepted July 12, 1993

Cell adhesion molecules TAX-1 (1), TAG-1 (2) and axonin-1(3) are homologous cell surface glycoproteins expressed in theneural tissue of human, rat and chicken respectively. They aremembers of a family of proteins composed of repeatedimmunoglobulm-Uke (IgC2) and fibronectin type m-Uke (FNUI)domains that ny^iatr- adhesion between components of thenervous system (4). Studies of neurite outgrowth on immobilizedaxonin-1 indicate that it participates in a heterophilic interactionwith LI, a related member of the immunoglobulin superfamilythat is expressed on the axons of migrating neurones (5).Recently, we demonstrated that mutations in the human LI genegive rise to X-linked hydrocephahis, a congenital disorder of braindevelopment (6, 7). In view of the structural similarity andfunctional association between LI and TAX-1 homologues weanticipate that disruption of TAX-1 would also result indevelopmental impairment. As a first step towards determiningwhether TAX-1 is associated with a genetically mapped inheriteddisorder we have established its chromosomal location.

Oligonudeotide primers specific for TAX-1 (EMBL accessionno. X68274) were used in pofymerase chain reactions (PCRs) to

amplify a 255 bp product from human DNA. Primers that flank thestop codon ("*^"n£r££pgiitg^gfltjy^ri forward and atccttgcgtgggtt-ctatcctgcg, reverse) were chosen in order to avoid introns. PCRsusing DNA from a panel of somatic cell hybrids indicated that theTAX-1 locus resides on chromosome 1 (Figure 1). Confirmationand refinement of this localization was obtained by fluorescent in situhybridization of a 4.5 kb TAX-1 cDNA clone to metaphasechromosomes. A single band of fluorescence was seen in all cellsin the proximal section of Iq32 (Iq32.1, Figure 2).

A literature search revealed that the gene for human myosin-binding protein H (MyBP-H), another member of the IgC2/FNHIrepeat family, resides within Iq32.1. More interesting, however,is the association of two morphogenetic abnormalities with thisregion. Van der Woude syndrome, a defect of craniofacialdevelopment thought to result from aberrant neural crest cellmigration, is genetically linked to Iq32.1 (8) and studies of deletionand translocation events indicate that a gene for microcephaly withmental retardation also resides in this region (9,10). In view of itspotential role in cell migration analysis of the TAX-1 gene in thesecases is warranted.

255bp-

Flgnrc 1. PCR amplification of 233 bp of the TAX-1 locus from genome DNA. PCRs otflized 10 ng of DNA, and 2 pmob of each primer in 10 pi commercialbuffer (Promega) with annealing at 65'C. Human fanes are labelled male and female. Rodent is a mixture of moose and hamster. The i M i y w a i of hybrids areshown above each lane, die primary mapping limMimome followed by nVtitirwal coiupouejs hi parentheses. ' - ' irvtirt— «n tnmmpiw .•iinmiimnfw V tracer|wrmrrtf« and 'm' a marker chromosome. 6-a pros 6-b repmcuu an entire 6. Pull details of the hybrids can be obtained from L.R. Molecular weight markers areHae m-digested *X174 and a 123 bp ladder.

To whom correspondence rfwuM be addretted

1462 Human Molecular Genetics, 1993, Vol 2, No. 9

Flpre 2. Fhxracent hybridization of TAX-1 cDNA to moiinhue chromoaonxifrom a male fympbobbutoid cell line wing the method of Fan et aL (11).

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