Thomas J. Kwiatkowski

Publications (4)10.6 Total impact

• Article: Identification and characterization of the gene causing type 1 spinocerebellar ataxia

  Sandro Banfi, Antonio Servadio, Ming-yi Chung, Thomas J. Kwiatkowski, Alanna E. McCall, Lisa A. Duvick, Ying Shen, Elizabeth J. Roth, Harry T. Orr, H.Y. Zoghbi
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  ABSTRACT: Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat. In this study, we describe the identification and characterization of the gene harbouring this repeat. The SCA1 transcript is 10,660 bases and is transcribed from both the wild type and SCA1 alleles. The CAG repeat, coding for a polyglutamine tract, lies within the coding region. The gene spans 450 kb of genomic DNA and is organized in nine exons. The first seven fall in the 5' untranslated region and the last two contain the coding region, and a 7,277 basepairs 3' untranslated region. The first four non−coding exons undergo alternative splicing in several tissues. These features suggest that the transcriptional and translational regulation of ataxin−1, the SCA1 encoded protein, may be complex.
  Nature Genetics. 07/1994; 7(4):513-520.
• Article: The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps centromeric to D6S89 and shows no recombination, in nine large kindreds, with a dinucleotide repeat at the AM10 locus

  Thomas J. Kwiatkowski, Harry T Orr, Sandro Banfi, Alanna E. McCall, Carla Jodice, Francesca Persichetti, Andrea Novelletto, Françoise LeBorgne-DeMarquoy, Lisa A. Duvick, Marina Frontali, S H Subramony, Arthur L Beaudet, Luciano Terrenato, Huda Y Zoghbi, Laura P W Ranum
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  ABSTRACT: Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder which is genetically linked to the short arm of chromosome 6, telomeric to the human major histocompatibility complex (HLA) and very close to D6S89. Previous multipoint linkage analysis using HLA, D6S89, and SCA1 suggested that SCA1 maps centromeric to D6S89. Data from this study using nine large kindreds indicate a maximum lod score between SCA1 and D6S89 of 67.58 at a maximum recombination fraction of .004. To localize SCA1 more precisely, we identified five dinucleotide polymorphisms near D6S89. Genotypic analyses at these polymorphic loci were carried out in nine multigeneration SCA1 kindreds and in the Centre d'Étude du Polymorphisme Humain reference families. A new marker, AM10GA, demonstrates no recombination with SCA1. The maximum lod score for AM10GA linkage to SCA1 is 42.14 at a recombination fraction of 0. Linkage analysis and analysis of recombination events confirm that SCA1 maps centromeric to D6S89 and establish the following order: CEN-D6S109–AM10GA/SCA1–D6S89–LR40–D6S202–TEL.
  The American Journal of Human Genetics 09/1993; · 10.60 Impact Factor
• Article: Rapid identification of yeast artificial chromosome clones by matrix pooling and crude Iysate PCR

  Thomas J. Kwiatkowski, Huda Y Zoghbi, Susan A. Ledbetter, Kimberly A. Ellison, A.Craig Chinault
• Article: Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1

  Harry T Orr, Ming-Yi Chung, Sandro Banfi, Thomas J. Kwiatkowski, Antonio Servadio, Arthur L Beaudet, Alanna E. McCall, Lisa A. Duvick, Laura P W Ranum, Huda Y Zoghbi