A study of restriction fragment length polymorphisms at the human alpha-1-antitrypsin locus

K. J. Matteson, Harry Ostrer, A. Chakravarti, K. H. Buetow, W. E. O'Brien, A. L. Beaudet, J. A. Phillips

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

A cloned cDNA for α-1-antitrypsin (α-1-AT) was selected from a human liver cDNA library. The identity of the clone was established by hybrid-selected translation and partial DNA sequencing. The cDNA was used as a probe to search for restriction site polymorphisms (RSPs) near the α-1-AT gene. Only two RSPs were found using 29 different restriction enzymes. Each of these polymorphisms resulted from the loss of a restriction site, one for EcoRI and the other for Taq I. The frequency of polymorphic restriction was calculated to be 1.1% to 2.6% of all sites tested, a figure lower than the 9.3% value observed for 12 RSPs in the human β-globin gene cluster. Since the corresponding figure for detectable polymorphisms at the α-1-AT locus at the protein level is 12%, restriction enzymes are comparatively inefficient in detecting genetic variability. The basis of this inefficiency was studied by computing the nucleotide diversity from the RSP data. On the average, one in 500 to 1000 bases is polymorphic around the α-1-At locus. This value is comparable to that which we have calculated for the human β-globin gene cluster and the human growth hormone gene cluster (both one in 500). These data demonstrate the limited usefulness of linked RSPs for genetic linkage studies at the α-1-AT locus.

Original languageEnglish (US)
Pages (from-to)263-267
Number of pages5
JournalHuman Genetics
Volume69
Issue number3
DOIs
StatePublished - Mar 1985
Externally publishedYes

Fingerprint

alpha 1-Antitrypsin
Multigene Family
Restriction Fragment Length Polymorphisms
Globins
Complementary DNA
Genetic Linkage
Human Growth Hormone
Enzymes
Gene Library
DNA Sequence Analysis
Nucleotides
Clone Cells
Liver
Genes
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Matteson, K. J., Ostrer, H., Chakravarti, A., Buetow, K. H., O'Brien, W. E., Beaudet, A. L., & Phillips, J. A. (1985). A study of restriction fragment length polymorphisms at the human alpha-1-antitrypsin locus. Human Genetics, 69(3), 263-267. https://doi.org/10.1007/BF00293037

A study of restriction fragment length polymorphisms at the human alpha-1-antitrypsin locus. / Matteson, K. J.; Ostrer, Harry; Chakravarti, A.; Buetow, K. H.; O'Brien, W. E.; Beaudet, A. L.; Phillips, J. A.

In: Human Genetics, Vol. 69, No. 3, 03.1985, p. 263-267.

Research output: Contribution to journalArticle

Matteson, KJ, Ostrer, H, Chakravarti, A, Buetow, KH, O'Brien, WE, Beaudet, AL & Phillips, JA 1985, 'A study of restriction fragment length polymorphisms at the human alpha-1-antitrypsin locus', Human Genetics, vol. 69, no. 3, pp. 263-267. https://doi.org/10.1007/BF00293037
Matteson, K. J. ; Ostrer, Harry ; Chakravarti, A. ; Buetow, K. H. ; O'Brien, W. E. ; Beaudet, A. L. ; Phillips, J. A. / A study of restriction fragment length polymorphisms at the human alpha-1-antitrypsin locus. In: Human Genetics. 1985 ; Vol. 69, No. 3. pp. 263-267.
@article{abfdbccd70f94174b6d2c0fe1c6bb8be,
title = "A study of restriction fragment length polymorphisms at the human alpha-1-antitrypsin locus",
abstract = "A cloned cDNA for α-1-antitrypsin (α-1-AT) was selected from a human liver cDNA library. The identity of the clone was established by hybrid-selected translation and partial DNA sequencing. The cDNA was used as a probe to search for restriction site polymorphisms (RSPs) near the α-1-AT gene. Only two RSPs were found using 29 different restriction enzymes. Each of these polymorphisms resulted from the loss of a restriction site, one for EcoRI and the other for Taq I. The frequency of polymorphic restriction was calculated to be 1.1{\%} to 2.6{\%} of all sites tested, a figure lower than the 9.3{\%} value observed for 12 RSPs in the human β-globin gene cluster. Since the corresponding figure for detectable polymorphisms at the α-1-AT locus at the protein level is 12{\%}, restriction enzymes are comparatively inefficient in detecting genetic variability. The basis of this inefficiency was studied by computing the nucleotide diversity from the RSP data. On the average, one in 500 to 1000 bases is polymorphic around the α-1-At locus. This value is comparable to that which we have calculated for the human β-globin gene cluster and the human growth hormone gene cluster (both one in 500). These data demonstrate the limited usefulness of linked RSPs for genetic linkage studies at the α-1-AT locus.",
author = "Matteson, {K. J.} and Harry Ostrer and A. Chakravarti and Buetow, {K. H.} and O'Brien, {W. E.} and Beaudet, {A. L.} and Phillips, {J. A.}",
year = "1985",
month = "3",
doi = "10.1007/BF00293037",
language = "English (US)",
volume = "69",
pages = "263--267",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - A study of restriction fragment length polymorphisms at the human alpha-1-antitrypsin locus

AU - Matteson, K. J.

AU - Ostrer, Harry

AU - Chakravarti, A.

AU - Buetow, K. H.

AU - O'Brien, W. E.

AU - Beaudet, A. L.

AU - Phillips, J. A.

PY - 1985/3

Y1 - 1985/3

N2 - A cloned cDNA for α-1-antitrypsin (α-1-AT) was selected from a human liver cDNA library. The identity of the clone was established by hybrid-selected translation and partial DNA sequencing. The cDNA was used as a probe to search for restriction site polymorphisms (RSPs) near the α-1-AT gene. Only two RSPs were found using 29 different restriction enzymes. Each of these polymorphisms resulted from the loss of a restriction site, one for EcoRI and the other for Taq I. The frequency of polymorphic restriction was calculated to be 1.1% to 2.6% of all sites tested, a figure lower than the 9.3% value observed for 12 RSPs in the human β-globin gene cluster. Since the corresponding figure for detectable polymorphisms at the α-1-AT locus at the protein level is 12%, restriction enzymes are comparatively inefficient in detecting genetic variability. The basis of this inefficiency was studied by computing the nucleotide diversity from the RSP data. On the average, one in 500 to 1000 bases is polymorphic around the α-1-At locus. This value is comparable to that which we have calculated for the human β-globin gene cluster and the human growth hormone gene cluster (both one in 500). These data demonstrate the limited usefulness of linked RSPs for genetic linkage studies at the α-1-AT locus.

AB - A cloned cDNA for α-1-antitrypsin (α-1-AT) was selected from a human liver cDNA library. The identity of the clone was established by hybrid-selected translation and partial DNA sequencing. The cDNA was used as a probe to search for restriction site polymorphisms (RSPs) near the α-1-AT gene. Only two RSPs were found using 29 different restriction enzymes. Each of these polymorphisms resulted from the loss of a restriction site, one for EcoRI and the other for Taq I. The frequency of polymorphic restriction was calculated to be 1.1% to 2.6% of all sites tested, a figure lower than the 9.3% value observed for 12 RSPs in the human β-globin gene cluster. Since the corresponding figure for detectable polymorphisms at the α-1-AT locus at the protein level is 12%, restriction enzymes are comparatively inefficient in detecting genetic variability. The basis of this inefficiency was studied by computing the nucleotide diversity from the RSP data. On the average, one in 500 to 1000 bases is polymorphic around the α-1-At locus. This value is comparable to that which we have calculated for the human β-globin gene cluster and the human growth hormone gene cluster (both one in 500). These data demonstrate the limited usefulness of linked RSPs for genetic linkage studies at the α-1-AT locus.

UR - http://www.scopus.com/inward/record.url?scp=0021963045&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021963045&partnerID=8YFLogxK

U2 - 10.1007/BF00293037

DO - 10.1007/BF00293037

M3 - Article

VL - 69

SP - 263

EP - 267

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 3

ER -