Publications in the Year: 1998

Journal Article

Baptista, {PMRV}.  1998.  Construction of a YAC/PAC physical map of a gene rich region in 1p13.3., jan. European Journal of Human Genetics. 6:168., Number NA: Springer Nature Abstract
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GROET, J, Ives {JH }, South {AP }, Baptista {PR }, Jones {TA }, Yaspo {ML }, Lehrach H, Potier {MC }, {Van Broeckhoven} C, Nizetic D.  1998.  Bacterial contig map of the 21q11 region associated with Alzheimer's disease and abnormal myelopoiesis in Down syndrome, jan. Genome Research. 8:385–398., Number 4: Cold Spring Harbor Laboratory Press Abstract

We present a high-resolution bacterial contig map of 3.4 Mb of genomic DNA in human chromosome 21q11-q21, encompassing the region of elevated disomic homozygosity in Down Syndrome-associated abnormal myelopoiesis and leukemia, as well as the markers, which has shown a strong association with Alzheimer's Disease that has never been explained. The map contains 89 overlapping PACs, BACs, or cosmids in three contigs (850, 850, and 1500 kb) with two gaps (one of 140-210 kb and the second < 5 kb). To date, eight transcribed sequences derived by cDNA selection, exon trapping, and/or global EST sequencing have been positioned onto the map, and the only two genes so far mapped to this cytogenetic region, STCH and RIP140 have been precisely localized. This work converts a further 10% of chromosome 21q into a high-resolution bacterial contig map, which will be the physical basis for the long-range sequencing of this region. The map will also enable positional derivation of new transcribed sequences, as well as new polymorphic probes, that will help in elucidation of the role the genes in this region may play in abnormal myelopoiesis and leukemia associated with trisomy 21 and Alzheimer's Disease.
Flomen, {RH }, Vatcheva R, Gorman {PA }, Baptista {PMRV}, Groet J.  1998.  Construction and analysis of a sequence-ready map in 4q25: Rieger syndrome can be caused by haploinsufficiency of RIEG, but also by chromosome breaks approximate to 90 kb upstream of this gene, feb. Genomics. 47:409–413., Number 3: Elsevier Abstract

The autosomal dominant disorder Rieger syndrome (RIEG) shows genetic heterogeneity and has a phenotype characterized by malformations of the anterior segment of the eye, failure of the periumbilical skin to involute, and dental hypoplasia. The main locus for RIEG was mapped to the 4q25-q27 chromosomal segment using a series of cytogenetic abnormalities as well as by genetic linkage to DNA markers. Recently, a bicoid-related homeobox transcription factor gene called RIEG has been cloned, characterized, and proven to cause the 4q25 linked RIEG. Its mode of action in the pathogenesis of RIEG was not conclusively proven, since most etiological mutations detected. In the RIEG sequence caused amino acid substitutions or splice changes in the homeodomain. Through FISH analysis of a 460-kb sequence-ready map (PAC contig) around RIEG that we report in this paper, we demonstrate that the 4q25 linked RIEG disorder can arise from the haploid, whole-gene deletion of RIEG, but also from a translocation break 90 kb upstream from the gene. The data provide conclusive evidence that physical or functional haploinsufficiency of RIEG is the pathogenic mechanism for Rieger syndrome. The map also defines restriction fragments bearing sequences with a potential key regulatory role in the control of homeobox gene expression.
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