Hereditary spastic paraplegia: LOD-score considerations for confirmation of linkage in a heterogeneous trait
- McGill Univ., Quebec (Canada); and others
Hereditary spastic paraplegia (HSP) is a degenerative disorder of the motor system, defined by progressive weakness and spasticity of the lower limbs. HSP may be inherited as an autosomal dominant (AD), autosomal recessive, or an X-linked trait. AD HSP is genetically heterogeneous, and three loci have been identified so far: SPG3 maps to chromosome 14q, SPG4 to 2p, and SPG4a to 15q. We have undertaken linkage analysis with 21 uncomplicated AD families to the three AD HSP loci. We report significant linkage for three of our families to the SPG4 locus and exclude several families by multipoint linkage. We used linkage information from several different research teams to evaluate the statistical probability of linkage to the SPG4 locus for uncomplicated AD HSP families and established the critical LOD-score value necessary for confirmation of linkage to the SPG4 locus from Bayesian statistics. In addition, we calculated the empirical P-values for the LOD scores obtained with all families with computer simulation methods. Power to detect significant linkage, as well as type I error probabilities, were evaluated. This combined analytical approach permitted conclusive linkage analyses on small to medium-size families, under the restrictions of genetic heterogeneity. 19 refs., 1 fig., 1 tab.
- OSTI ID:
- 518548
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 3 Vol. 60; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
Similar Records
Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q
Linkage of the late onset autosomal dominant familial spastic paraplegia (DFSPII) to chromosome 2p markers
Related Subjects
BASIC STUDIES
99 GENERAL AND MISCELLANEOUS
BIOLOGICAL MARKERS
COMPUTERIZED SIMULATION
DOMINANT MUTATIONS
ERRORS
F CODES
GENES
GENETIC MAPPING
GENETICS
GENOTYPE
HEREDITARY DISEASES
HUMAN CHROMOSOME 14
HUMAN CHROMOSOME 15
HUMAN CHROMOSOME 2
NERVOUS SYSTEM DISEASES
PATIENTS
POLYMERASE CHAIN REACTION
PROBABILISTIC ESTIMATION
RECESSIVE MUTATIONS
STATISTICS