The identification of five novel genes in the cri-du-chat critical region

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134475

Simmons, A D; Gallardo, T D; Lovett, M ^[1]

---

1. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); and others

Cri-du-chat is a contiguous gene syndrome associated with deletions in the short arm of chromosome 5 (chr 5). Chr 5p-specific markers have been used to define two critical regions: a larynx malformation region, located at 5p15.3, and a region responsible for the remaining clinical features of the syndrome, which maps to 5p15.2. Thirty cosmids that map to this latter region have been isolated from the LANL chr 5-specific library using 5 STSs. More recently, we have constructed a YAC contig of the region which encompasses 2-3 Mb. The 30 framework cosmids were used in a direct selection with cDNAs from placenta, activated T-cells and cerebellum to isolate an initial set of expressed sequences from this region. Since no genes, to date, have been isolated or localized within the cri-du-chat deletion, a cosmid containing a control reporter gene (ANX6) was used to monitor enrichment. ANX6 cDNAs were enriched by several thousand-fold in the selected cDNAs. A total of nine non overlapping cDNA fragments were obtained from the cDNA pools. These have been ordered within the YAC contig, map to 5 discrete cosmid sets in the critical region and thus conservatively represent five discrete transcription units. The DNA sequences of these fragments are novel by sequence database comparisons. PCR primers were constructed and were used to confirm gene placements in the YAC contig, as well as to investigate the expression profile of these genes in several different tissues and cell types. In one case, these primer sets enabled two of the nine fragments to be linked into a larger cDNA. The nine cDNAs showed various patterns of differential expression in a panel of tissues. These expressed sequences represent the first genes isolated within the cri-du-chat critical region and represent the initial steps in the derivation of a comprehensive inventory and expression profile of the estimated 100 genes that may reside in this region.

• OSTI ID: 134475
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
CONGENITAL MALFORMATIONS
CONTIGS
DNA
DNA SEQUENCING
FRAGMENTATION
GENE REGULATION
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 5
PATIENTS
PHENOTYPE
POLYMERASE CHAIN REACTION
TRANSCRIPTION
YEASTS