Genetic heterogeneity in tuberous sclerosis

Janssen, L. A. J.; Sandkuyl, L. A.; Merkens, E. C.; Maat-Kievit, J.A.; Sampson, Julian R.; Fleury, P; Hennekam, Raoul C. M.; Grosveld, Gerard; Lindhout, Dick; Halley, Dicky

doi:10.1016/0888-7543(90)90277-2

Cited by 49 publications

(21 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data of Kandt et al (1989) on 9 families exclude linkage of ABO to tuberous sclerosis for a distance of 20cM. The data of Smith et al (1990) support the existence of a single locus on chromosome 11, while Janssen (1990) found evidence for heterogeneity with a TSC gene on 9 in some families and 11 in others. A collaborative effort in which 111 families from many sources were analysed in several different ways concluded that there is definitely a gene on 9q in the region of ABL and also a gene on 1 lq, but that the existence of yet another TSC locus cannot be excluded (Haines , 1990).…”

Section: New Loci On Chromosomesupporting

confidence: 49%

Report of the committee on the genetic constitution of chromosome 9

Povey¹,

Goudie²,

Porter³

1990

Cytogenet Genome Res

View full text Add to dashboard Cite

Section: New Loci On Chromosomesupporting

confidence: 49%

Report of the committee on the genetic constitution of chromosome 9

Povey¹,

Goudie²,

Porter³

1990

Cytogenet Genome Res

View full text Add to dashboard Cite

“…The procedure can be applied to map one single locus in the presence of unlinked families, two loci on one chromosome, or even for the com bined analysis of two or more dispersed chro mosomal regions. The latter application has been introduced as 'imaginary chromosome approach' (ICA) [4], The support for linkage and heterogeneity in a given family is usually calculated via the following equation, which was implemented in the HOMOG programs by Ott [3]:…”

Section: Introductionmentioning

confidence: 99%

Linkage Analysis under Locus Heterogeneity: Behaviour of the A-Test in Complex Analyses

Janssen

Halley²,

Sandkuijl³

1997

Hum Hered

View full text Add to dashboard Cite

The admixture test (A-test) is a popular method for the analysis of linkage data when locus heterogeneity is suspected. It can be applied on pairwise linkage data, multipoint data and even for the simultaneous analysis of data from multiple dispersed candidate regions. However, very little is known about the conditions for the use of the method under these divergent circumstances. By performing analytical evaluations, we demonstrate that the A-test is inconsistent if there is a relationship between the phenotype and the probability of being linked. Biased estimates of the recombination fraction (Θ) and the proportion of linked families (α) may occur if the actual frequency of linked families is not identical among small and large families. We conclude that the A-test should be used with caution if the phenotype and the probability of developing the phenotype at a certain age cannot be shown to be equal for family members of linked and unlinked families. If dissimilarities in family size cannot be ruled out, the extent of bias should be considered and size specific α-values should be used in risk calculations.

show abstract

“…'6 Loci were ordered as shown in fig 2 Key recombination events on the disease conferring chromosome occur between ABO and DBH, and GSN and D9S60, in unaffected subjects III-3 and III 9 respectively, positioning TSCJ proximal to DBH and distal to GSN. DBH is the closest distal flanking marker so far proposed for TSC1.…”

mentioning

confidence: 99%

Identification of markers flanking the tuberous sclerosis locus on chromosome 9 (TSC1).

Nellist

Brook-Carter

Connor

et al. 1993

Journal of Medical Genetics

View full text Add to dashboard Cite

Analysis of a large tuberous sclerosis pedigree confirmed linkage to a locus on the long arm of chromosome 9, with recombination events placing the disease gene distal to gelsolin and proximal to dopamine fJ-hydroxylase. (J Med Genet 1993;30:224-7) Linkage analysis in tuberous sclerosis (TSC) is complicated by locus heterogeneity,'2 making it difficult to distinguish recombination from non-linkage and to identify appropriate flanking markers. The problem is exacerbated by the paucity of large affected pedigrees.Despite these difficulties a number of studies have established the existence of a TSC locus on distal 9q (TSC1) and have used a variety of analytical approaches to define confidence intervals for the position of this locus."4 However, the validity of these approaches is undetermined and therefore haplotype analysis in large pedigrees which independently

show abstract

Genetic heterogeneity in tuberous sclerosis

Cited by 49 publications

References 17 publications

Report of the committee on the genetic constitution of chromosome 9

Report of the committee on the genetic constitution of chromosome 9

Linkage Analysis under Locus Heterogeneity: Behaviour of the A-Test in Complex Analyses

Identification of markers flanking the tuberous sclerosis locus on chromosome 9 (TSC1).

Contact Info

Product

Resources

About