The effect of parental gender on the GAA dynamic mutation in the FRDA gene

Journal Article · Sat Feb 01 00:00:00 EST 1997 · American Journal of Human Genetics

OSTI ID:518527

Pianese, L; Cavalcanti, F; Calabrese, O ^[1]

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1. Federico II Univ., Naples (Italy)

Within a cooperative study, we recently isolated the defective gene (X25) causing Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disorder. X25 encodes a 210-amino acid protein, frataxin, whose function is unknown. Frataxin mRNA levels are reduced in FRDA patients. The most frequent mutation is the expansion of a (GAA){sub n} trinucleotide repeat in the first X25 intron. Normal chromosomes contain 8-22 copies of the triplet, whereas FRDA chromosomes contain >200 copies. In addition, we described few patients with point mutations. The expansion of trinucleotide repeats has been previously demonstrated to be the mutational mechanism associated with eight human diseases. Trinucleotide repeats occur both in coding and noncoding regions of the gene. Although trinucleotide repeats in the normal size range are relatively stable, expanded repeats are highly variable when transmitted from one generation to the next. For the eight previously described diseases, meiotic instability is generally associated with a mutational bias toward an increase in repeat number. Here, we analyze intergenerational variability in FRDA chromosomes in parent-carrier child pairs. In addition, we studied the stability of FRDA expanded alleles in male gametogenesis, directly analyzing male germ cells. 9 refs., 3 figs., 1 tab.

• OSTI ID: 518527
• Journal Information: American Journal of Human Genetics, Vol. 60, Issue 2; Other Information: PBD: Feb 1997
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
GENES
GENE MUTATIONS
MUTATION FREQUENCY
DNA SEQUENCING
SEX DEPENDENCE
GENETICS
PATIENTS
HEREDITARY DISEASES
NERVOUS SYSTEM DISEASES
HUMAN CHROMOSOMES
MEIOSIS
GENETIC VARIABILITY
GAMETOGENESIS
GENETIC EFFECTS
AMINO ACIDS
RECESSIVE MUTATIONS
NUCLEOTIDES
INTRONS
GERM CELLS
POLYMERASE CHAIN REACTION