Identification and Chromosomal Localization of Human Genes Containing CAG/CTG Repeats Expressed in Testis and Brain

Abstract

Human genes containing triplet repeats have been demonstrated to be involved in several neurodegenerative diseases by expansion of the repeat in succeeding generations. To identify novel genes involved in such pathologies, we have isolated transcripts containing (CAG/CTG)n repeats using two approaches. First, we screened 4 × 106 clones representing 10 copies of a human testis cDNA library using a (CAG)14 oligonucleotide probe. Among the 910 clones identified, the 243 clones with the strongest hybridization signal were sequenced partially from 3′ or 5′ ends. This provided us with 251 partial sequences that grouped into clusters corresponding to 39 genes, of which 19 represent unknown species. Second, we selected 203 additional ESTs containing (CAG/CTG)n repeats representing 121 clusters from the IMAGE consortium infant brain cDNA library. From these two series of sequences, we have localized 95 genes on human chromosomes using a panel of whole genome radiation hybrid (Genebridge 4). These genes are located on all of the chromosomes except for chromosome X, the highest density being observed on chromosome 19.[The sequence data described in this paper have been submitted to GenBank under accession nos. AA065241–AA065346.]

Homologs of the Yeast Longevity Gene LAG1 in Caenorhabditis elegans and Human

“…The repeats expand in successive generations (Aslanidis et al 1992). These genes are expressed in brain and testis frequently (Bulle et al 1997). A search for novel disease genes in human testis and infant brain cDNA libraries has localized 95 genes that contain (CAG/CTG) n repeats, with the highest density on chromosome 19 (Bulle et al 1997).…”

“…These genes are expressed in brain and testis frequently (Bulle et al 1997). A search for novel disease genes in human testis and infant brain cDNA libraries has localized 95 genes that contain (CAG/CTG) n repeats, with the highest density on chromosome 19 (Bulle et al 1997). LAG1Hs contains a repeat of four CTGs in its coding region and similarity in tissue expression profile to these genes.…”

Detection of polyglutamine expansion in a new acidic protein: a candidate for childhood onset schizophrenia?

“…One of the proteins, DAN26, showed a theoretical mass in the 50-60 kDa range (52.5 kDa) and theoretical pI in the 4-6 range (pI 4.8), and was retained for PCR screening in COS family NFI. Polymorphic and/or long CAG repeats (n = 20) consisting of more than 10 consecutive units and previously found in human cDNA libraries [15][16][17] were also tested including 2.116, 2.119, i.181, i.182, 15 12501r, b01500t, and g02502r, 16 and CTG1a, CTG3a, CTG4a, CTG7a, CTG20a, CAGF9, F28, H1, H16, H26, H32, H38, H39, H44, H45, L69, L85, L114, L234, and L237, some of them predicted to code for a polygln stretch. 17 Finally, seven CAG/CTG repeats (GCT1C9, GCT4B10, GCT5E11, GCT16E06, GCT10D04, GCT10C10, and GCT10H06) isolated from genomic DNA and consisting of more than 15 consecutive units were tested as well.…”

“…Twenty-seven CAG repeats found in cDNAs [15][16][17] and CAG/CTG repeats isolated from genomic DNA 18 consisting of more than 10-15 consecutive units were also tested for expansion in NFI (see Methods). All the candidates tested showed unenlarged CAG repeat alleles, and no difference in the size Figure 1 Detection of PGE in COS. Electrophoresis was performed on 50 g (4-20% polyacrylamide gradient gels) or 60 g (long 10% polyacrylamide gels) of protein from LCL extracts (see Table 1).…”

Sporadic testicular germ cell cancers do not exhibit specific alteration in CAG/CTG repeats containing genes expressed in human testis

“…We identi®ed 352 positive clones corresponding to 65 di erent genes (Bulle et al, 1997;Pawlak et al, 1998). Among them, 32 contained more than four CAG/CTG repeats which were framed by sequences allowing the design of primers for further ampli®cation.…”