Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome

Stephen N Thibodeau, H. R. Dorkins, K. R. Faulk, R. Berry, A. C M Smith, R. Hagerman, A. King, K. E. Davies

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Linkage data, using the polymorphic markers 52A (DXS51), F9, 4D-8(DXS98), and St14(DXS52), are presented from 14 fragile X pedigrees and from 7 normal pedigrees derived from the collection of the Centre d'Étude du Polymorphisme Humaine. A multipoint linkage analysis indicates that the most probable order of these four loci in normal families is DXS51-F9-DXS98-DXS52. Recombination frequencies ( {Mathematical expression}) corresponding to maximum LOD scores ( {Mathematical expression}) were obtained by two-point linkage analysis for a nuber of linkage groups, including: DXS51-F9 ( {Mathematical expression}=5.94, {Mathematical expression}=0.03), F9-DXS98 ( {Mathematical expression}=0.51, {Mathematical expression}=0.26), F9-DXS52 ( {Mathematical expression}=0.84, {Mathematical expression}=0.27), and DXS98-DXS52 ( {Mathematical expression}=0.32, {Mathematical expression}=0.20). A multipoint linkage analysis of these loci, including the fragile X locus, was also performed for the fragile X population and the data support the relative order (DSX51, F9, DXS98)-FRAXA-DXS52. Recombination frequencies and maximum LOD scores, which again were derived from two-point linkage analyses, were obtained for the linkage groups DXS51-F9 ( {Mathematical expression}=9.96, {Mathematical expression}=0) and F9-DXS52 ( {Mathematical expression}=0.07, {Mathematical expression}=0.45), as well as for the groups DXS51-FRAXA ( {Mathematical expression}=2.42, {Mathematical expression}=0.15), F9-FRAXA ( {Mathematical expression}=1.30, {Mathematical expression}=0.18), DXS98-FRAXA ( {Mathematical expression}=0.05 {Mathematical expression}=0.36), and DXS52-FRAXA ( {Mathematical expression}=2.42 {Mathematical expression}=0.15). The linkage data was further tested for the presence of genetic heterogeneity both within and between the fragile X and normal families for the intervals DXS51-F9, F9-DXS52, F9-FRAXA, and DXS52-FRAXA using a modification of the A test. Except for the interval F9-FRAXA (P<0.10) there was no evidence of genetic heterogeneity for each of the various linkage groups examined. The heterogeneity detected for the interval F9-FRAXA, however, was most likely due to one family (Fx-28) that displayed very tight linkage between these two loci.

Original languageEnglish (US)
Pages (from-to)219-227
Number of pages9
JournalHuman Genetics
Volume79
Issue number3
DOIs
StatePublished - Jul 1988
Externally publishedYes

Fingerprint

Fragile X Syndrome
Genetic Heterogeneity
Information Storage and Retrieval
Pedigree
Genetic Markers
Genetic Recombination
Population

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Thibodeau, S. N., Dorkins, H. R., Faulk, K. R., Berry, R., Smith, A. C. M., Hagerman, R., ... Davies, K. E. (1988). Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome. Human Genetics, 79(3), 219-227. https://doi.org/10.1007/BF00366240

Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome. / Thibodeau, Stephen N; Dorkins, H. R.; Faulk, K. R.; Berry, R.; Smith, A. C M; Hagerman, R.; King, A.; Davies, K. E.

In: Human Genetics, Vol. 79, No. 3, 07.1988, p. 219-227.

Research output: Contribution to journalArticle

Thibodeau, SN, Dorkins, HR, Faulk, KR, Berry, R, Smith, ACM, Hagerman, R, King, A & Davies, KE 1988, 'Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome', Human Genetics, vol. 79, no. 3, pp. 219-227. https://doi.org/10.1007/BF00366240
Thibodeau, Stephen N ; Dorkins, H. R. ; Faulk, K. R. ; Berry, R. ; Smith, A. C M ; Hagerman, R. ; King, A. ; Davies, K. E. / Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome. In: Human Genetics. 1988 ; Vol. 79, No. 3. pp. 219-227.
@article{2599e38c83fc4fe9a2872cc17d80a904,
title = "Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome",
abstract = "Linkage data, using the polymorphic markers 52A (DXS51), F9, 4D-8(DXS98), and St14(DXS52), are presented from 14 fragile X pedigrees and from 7 normal pedigrees derived from the collection of the Centre d'{\'E}tude du Polymorphisme Humaine. A multipoint linkage analysis indicates that the most probable order of these four loci in normal families is DXS51-F9-DXS98-DXS52. Recombination frequencies ( {Mathematical expression}) corresponding to maximum LOD scores ( {Mathematical expression}) were obtained by two-point linkage analysis for a nuber of linkage groups, including: DXS51-F9 ( {Mathematical expression}=5.94, {Mathematical expression}=0.03), F9-DXS98 ( {Mathematical expression}=0.51, {Mathematical expression}=0.26), F9-DXS52 ( {Mathematical expression}=0.84, {Mathematical expression}=0.27), and DXS98-DXS52 ( {Mathematical expression}=0.32, {Mathematical expression}=0.20). A multipoint linkage analysis of these loci, including the fragile X locus, was also performed for the fragile X population and the data support the relative order (DSX51, F9, DXS98)-FRAXA-DXS52. Recombination frequencies and maximum LOD scores, which again were derived from two-point linkage analyses, were obtained for the linkage groups DXS51-F9 ( {Mathematical expression}=9.96, {Mathematical expression}=0) and F9-DXS52 ( {Mathematical expression}=0.07, {Mathematical expression}=0.45), as well as for the groups DXS51-FRAXA ( {Mathematical expression}=2.42, {Mathematical expression}=0.15), F9-FRAXA ( {Mathematical expression}=1.30, {Mathematical expression}=0.18), DXS98-FRAXA ( {Mathematical expression}=0.05 {Mathematical expression}=0.36), and DXS52-FRAXA ( {Mathematical expression}=2.42 {Mathematical expression}=0.15). The linkage data was further tested for the presence of genetic heterogeneity both within and between the fragile X and normal families for the intervals DXS51-F9, F9-DXS52, F9-FRAXA, and DXS52-FRAXA using a modification of the A test. Except for the interval F9-FRAXA (P<0.10) there was no evidence of genetic heterogeneity for each of the various linkage groups examined. The heterogeneity detected for the interval F9-FRAXA, however, was most likely due to one family (Fx-28) that displayed very tight linkage between these two loci.",
author = "Thibodeau, {Stephen N} and Dorkins, {H. R.} and Faulk, {K. R.} and R. Berry and Smith, {A. C M} and R. Hagerman and A. King and Davies, {K. E.}",
year = "1988",
month = "7",
doi = "10.1007/BF00366240",
language = "English (US)",
volume = "79",
pages = "219--227",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome

AU - Thibodeau, Stephen N

AU - Dorkins, H. R.

AU - Faulk, K. R.

AU - Berry, R.

AU - Smith, A. C M

AU - Hagerman, R.

AU - King, A.

AU - Davies, K. E.

PY - 1988/7

Y1 - 1988/7

N2 - Linkage data, using the polymorphic markers 52A (DXS51), F9, 4D-8(DXS98), and St14(DXS52), are presented from 14 fragile X pedigrees and from 7 normal pedigrees derived from the collection of the Centre d'Étude du Polymorphisme Humaine. A multipoint linkage analysis indicates that the most probable order of these four loci in normal families is DXS51-F9-DXS98-DXS52. Recombination frequencies ( {Mathematical expression}) corresponding to maximum LOD scores ( {Mathematical expression}) were obtained by two-point linkage analysis for a nuber of linkage groups, including: DXS51-F9 ( {Mathematical expression}=5.94, {Mathematical expression}=0.03), F9-DXS98 ( {Mathematical expression}=0.51, {Mathematical expression}=0.26), F9-DXS52 ( {Mathematical expression}=0.84, {Mathematical expression}=0.27), and DXS98-DXS52 ( {Mathematical expression}=0.32, {Mathematical expression}=0.20). A multipoint linkage analysis of these loci, including the fragile X locus, was also performed for the fragile X population and the data support the relative order (DSX51, F9, DXS98)-FRAXA-DXS52. Recombination frequencies and maximum LOD scores, which again were derived from two-point linkage analyses, were obtained for the linkage groups DXS51-F9 ( {Mathematical expression}=9.96, {Mathematical expression}=0) and F9-DXS52 ( {Mathematical expression}=0.07, {Mathematical expression}=0.45), as well as for the groups DXS51-FRAXA ( {Mathematical expression}=2.42, {Mathematical expression}=0.15), F9-FRAXA ( {Mathematical expression}=1.30, {Mathematical expression}=0.18), DXS98-FRAXA ( {Mathematical expression}=0.05 {Mathematical expression}=0.36), and DXS52-FRAXA ( {Mathematical expression}=2.42 {Mathematical expression}=0.15). The linkage data was further tested for the presence of genetic heterogeneity both within and between the fragile X and normal families for the intervals DXS51-F9, F9-DXS52, F9-FRAXA, and DXS52-FRAXA using a modification of the A test. Except for the interval F9-FRAXA (P<0.10) there was no evidence of genetic heterogeneity for each of the various linkage groups examined. The heterogeneity detected for the interval F9-FRAXA, however, was most likely due to one family (Fx-28) that displayed very tight linkage between these two loci.

AB - Linkage data, using the polymorphic markers 52A (DXS51), F9, 4D-8(DXS98), and St14(DXS52), are presented from 14 fragile X pedigrees and from 7 normal pedigrees derived from the collection of the Centre d'Étude du Polymorphisme Humaine. A multipoint linkage analysis indicates that the most probable order of these four loci in normal families is DXS51-F9-DXS98-DXS52. Recombination frequencies ( {Mathematical expression}) corresponding to maximum LOD scores ( {Mathematical expression}) were obtained by two-point linkage analysis for a nuber of linkage groups, including: DXS51-F9 ( {Mathematical expression}=5.94, {Mathematical expression}=0.03), F9-DXS98 ( {Mathematical expression}=0.51, {Mathematical expression}=0.26), F9-DXS52 ( {Mathematical expression}=0.84, {Mathematical expression}=0.27), and DXS98-DXS52 ( {Mathematical expression}=0.32, {Mathematical expression}=0.20). A multipoint linkage analysis of these loci, including the fragile X locus, was also performed for the fragile X population and the data support the relative order (DSX51, F9, DXS98)-FRAXA-DXS52. Recombination frequencies and maximum LOD scores, which again were derived from two-point linkage analyses, were obtained for the linkage groups DXS51-F9 ( {Mathematical expression}=9.96, {Mathematical expression}=0) and F9-DXS52 ( {Mathematical expression}=0.07, {Mathematical expression}=0.45), as well as for the groups DXS51-FRAXA ( {Mathematical expression}=2.42, {Mathematical expression}=0.15), F9-FRAXA ( {Mathematical expression}=1.30, {Mathematical expression}=0.18), DXS98-FRAXA ( {Mathematical expression}=0.05 {Mathematical expression}=0.36), and DXS52-FRAXA ( {Mathematical expression}=2.42 {Mathematical expression}=0.15). The linkage data was further tested for the presence of genetic heterogeneity both within and between the fragile X and normal families for the intervals DXS51-F9, F9-DXS52, F9-FRAXA, and DXS52-FRAXA using a modification of the A test. Except for the interval F9-FRAXA (P<0.10) there was no evidence of genetic heterogeneity for each of the various linkage groups examined. The heterogeneity detected for the interval F9-FRAXA, however, was most likely due to one family (Fx-28) that displayed very tight linkage between these two loci.

UR - http://www.scopus.com/inward/record.url?scp=0023751681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023751681&partnerID=8YFLogxK

U2 - 10.1007/BF00366240

DO - 10.1007/BF00366240

M3 - Article

VL - 79

SP - 219

EP - 227

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 3

ER -