Rapid genetic analysis of families with polycystic kidney disease 1 by means of a microsatellite marker

P. C. Harris; S. Thomas; P. J. Ratcliffe; M. H. Breuning; E. Coto; C. Lopez-Larrea

doi:10.1016/0140-6736(91)92300-Q

Rapid genetic analysis of families with polycystic kidney disease 1 by means of a microsatellite marker

P. C. Harris, S. Thomas, P. J. Ratcliffe, M. H. Breuning, E. Coto, C. Lopez-Larrea

Nephrology and Hypertension

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

Abstract

Presymptomatic diagnosis of polycystic kidney disease 1 (PKD1) is possible by genetic linkage analysis with markers from both sides of the disease locus. The existing proximal markers are not informative in many families, so such analysis is difficult and time-consuming. We sought more useful length polymorphisms on the proximal side of the locus among simple sequence repeats (microsatellites). We identified two microsatellite polymorphisms that lie closer to the PKD1 locus than any previously described highly variable marker. One, SM7, is especially informative; we have found fourteen alleles and the observed heterozygosity in caucasians is 62·7%. Genetic linkage analysis in PKD1 families suggests that both of the markers lie proximal to the disease gene, closer than existing flanking markers. These polymorphisms can be simply assayed by polymerase chain reaction amplification of the variable regions, which generates DNA fragments that can be separated on non-denaturing acrylamide gels and directly examined after gel staining. This rapid, inexpensive, and non-radioactive method of linkage analysis allows the complete study of DNA samples within 8 h.

Original language	English (US)
Pages (from-to)	1484-1487
Number of pages	4
Journal	The Lancet
Volume	338
Issue number	8781
DOIs	https://doi.org/10.1016/0140-6736(91)92300-Q
State	Published - Dec 14 1991

ASJC Scopus subject areas

General Medicine

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title = "Rapid genetic analysis of families with polycystic kidney disease 1 by means of a microsatellite marker",

abstract = "Presymptomatic diagnosis of polycystic kidney disease 1 (PKD1) is possible by genetic linkage analysis with markers from both sides of the disease locus. The existing proximal markers are not informative in many families, so such analysis is difficult and time-consuming. We sought more useful length polymorphisms on the proximal side of the locus among simple sequence repeats (microsatellites). We identified two microsatellite polymorphisms that lie closer to the PKD1 locus than any previously described highly variable marker. One, SM7, is especially informative; we have found fourteen alleles and the observed heterozygosity in caucasians is 62·7%. Genetic linkage analysis in PKD1 families suggests that both of the markers lie proximal to the disease gene, closer than existing flanking markers. These polymorphisms can be simply assayed by polymerase chain reaction amplification of the variable regions, which generates DNA fragments that can be separated on non-denaturing acrylamide gels and directly examined after gel staining. This rapid, inexpensive, and non-radioactive method of linkage analysis allows the complete study of DNA samples within 8 h.",

author = "Harris, {P. C.} and S. Thomas and Ratcliffe, {P. J.} and Breuning, {M. H.} and E. Coto and C. Lopez-Larrea",

note = "Funding Information: We thank Dr Y. Nakamura and Dr G. G. Germino for DNA probes; Dr R. L. Stallings for the cosmid library; Dr C. G. Winearls and Dr D. 0. Oliver for permission to study their patients; Dr M. H. R. Sheriff, Dr S. Tan, and Dr D. R. Higgs for Sri Lankan DNA samples. Ms L. Rose for expert typing; Dr S. Aquado for clinical analysis of the Spanish family; Dr J. A. Todd for advice on CA repeats; Dr D. R. Higgs for stimulating discussions and constructive comments; and Prof D. J. Weatherall for continued support and helpful scrutiny of the paper. This study was supported by the Medical Research Council, the Wellcome Trust, and the Spanish Institute of Health. Coordination of research was aided by the EC Concerted Action {"}Toward prevention of kidney failure caused by inherited polycystic kidney disease{"}.",

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doi = "10.1016/0140-6736(91)92300-Q",

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T1 - Rapid genetic analysis of families with polycystic kidney disease 1 by means of a microsatellite marker

AU - Harris, P. C.

AU - Thomas, S.

AU - Ratcliffe, P. J.

AU - Breuning, M. H.

AU - Coto, E.

AU - Lopez-Larrea, C.

N1 - Funding Information: We thank Dr Y. Nakamura and Dr G. G. Germino for DNA probes; Dr R. L. Stallings for the cosmid library; Dr C. G. Winearls and Dr D. 0. Oliver for permission to study their patients; Dr M. H. R. Sheriff, Dr S. Tan, and Dr D. R. Higgs for Sri Lankan DNA samples. Ms L. Rose for expert typing; Dr S. Aquado for clinical analysis of the Spanish family; Dr J. A. Todd for advice on CA repeats; Dr D. R. Higgs for stimulating discussions and constructive comments; and Prof D. J. Weatherall for continued support and helpful scrutiny of the paper. This study was supported by the Medical Research Council, the Wellcome Trust, and the Spanish Institute of Health. Coordination of research was aided by the EC Concerted Action "Toward prevention of kidney failure caused by inherited polycystic kidney disease".

PY - 1991/12/14

Y1 - 1991/12/14

N2 - Presymptomatic diagnosis of polycystic kidney disease 1 (PKD1) is possible by genetic linkage analysis with markers from both sides of the disease locus. The existing proximal markers are not informative in many families, so such analysis is difficult and time-consuming. We sought more useful length polymorphisms on the proximal side of the locus among simple sequence repeats (microsatellites). We identified two microsatellite polymorphisms that lie closer to the PKD1 locus than any previously described highly variable marker. One, SM7, is especially informative; we have found fourteen alleles and the observed heterozygosity in caucasians is 62·7%. Genetic linkage analysis in PKD1 families suggests that both of the markers lie proximal to the disease gene, closer than existing flanking markers. These polymorphisms can be simply assayed by polymerase chain reaction amplification of the variable regions, which generates DNA fragments that can be separated on non-denaturing acrylamide gels and directly examined after gel staining. This rapid, inexpensive, and non-radioactive method of linkage analysis allows the complete study of DNA samples within 8 h.

AB - Presymptomatic diagnosis of polycystic kidney disease 1 (PKD1) is possible by genetic linkage analysis with markers from both sides of the disease locus. The existing proximal markers are not informative in many families, so such analysis is difficult and time-consuming. We sought more useful length polymorphisms on the proximal side of the locus among simple sequence repeats (microsatellites). We identified two microsatellite polymorphisms that lie closer to the PKD1 locus than any previously described highly variable marker. One, SM7, is especially informative; we have found fourteen alleles and the observed heterozygosity in caucasians is 62·7%. Genetic linkage analysis in PKD1 families suggests that both of the markers lie proximal to the disease gene, closer than existing flanking markers. These polymorphisms can be simply assayed by polymerase chain reaction amplification of the variable regions, which generates DNA fragments that can be separated on non-denaturing acrylamide gels and directly examined after gel staining. This rapid, inexpensive, and non-radioactive method of linkage analysis allows the complete study of DNA samples within 8 h.

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Rapid genetic analysis of families with polycystic kidney disease 1 by means of a microsatellite marker

Abstract

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