摘要:

The aim of this paper is to clarify some of the concepts used in the calculation of risk in genetic counselling. The use of probability as a measure of risk in a particular case is reviewed, with special reference to the Fisher ‐ Neyman controversy. The technical concept of likelihood is then introduced and applied to risk probabilities themselves. The difficulties of interpretation are discussed, with a distinction drawn between calculating the risk for a child and inferring the genotype of his mother, even though the risk is wholly determined by the genotype. Fiducial inference is briefly mentioned, and the paper ends with a discussion of the problem which arises when the functional relationship between an unknown parameter and the unknown risk is not 1:1. The conclusion is tentatively reached that risk can only be gauged by probability and thus that prior probabilities must sometimes be assumed, but the paper is primarily intended as a guide and catalyst for the informed discussion of some of the difficulties, which may involve ethical dilemma

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1989.tb03192.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

In a material of 26 Caucasian families, 23 with at least 2 children affected with Batten disease, we found a lod score of 3.00 at theta=0.00 in males and theta=0.26 in females with haptoglobin (HP), and assign the locus for Batten disease to 16q22.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1989.tb03193.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Hobbs et al. (N. Engl. J. Med. 317: 734–737, 1987) reported a large deletion of approximately 10 kilobases in the 5′ portion of the human low‐density lipoprotein (LDL) receptor gene. This deletion affects about 60% of familial hypercholesterolemia (FH) heterozygotes in the French Canadian population. We have developed a rapid, convenient method for the detection of the deletion using double digestion with the restriction enzymes Xbal and EcoRV, or triple digestion with Xbal, EcoRV and XmnI, and a 650 bp cDNA probe, radio‐labeled using a random oligonucleotide primer technique. Eighty French Canadian FH heterozygotes were screened for the presence of the deletion. Forty‐seven (59%) of them were found to carry the 10 kb deletion. Using the same method, we also identified a new mutation which was found in four of the 80 (5%) FH patients. This mutation has been found to be a 5 kb deletion removing exons 2 and 3 of the LDL receptor gene, which correspond to the first two repeats of the LDL receptor binding domain. Cosegregation of the 5 kb deletion and the FH phenotype was observed in one family. Possible structure‐function relationship i

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1989.tb03194.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Associations have been reported between restriction fragment length polymorphisms (RFLPs) at fibrinogen loci and plasma fibrinogen concentration, in a British study. We have examined a series of unrelated Norwegians. We found no association between plasma fibrinogen concentration and any genotype in either of two fibrinogen polymorphisms examined (one at the α‐fibrinogen locus, the other at the β‐fibrinogen locus). We have also examined monozygotic twins and evaluated heritability of fibrinogen level by the intraclass correlation coefficient. We arrived at an unimpressive estimate of heritability. With such a low level of heritability, it would have been surprising if we had found an association with a single gene marker in a relatively limited series of people. The reason for the discrepancy between the British and the Norwegian study is unknown. Great care has to be exercised in interpreting disease associations, since with DNA variations being examined at an increasing number of “candidate loci”, the risk of finding spurious associations increases with the number of analyses

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1989.tb03195.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

This report gives a description of a three‐generation family in which spondylocostal dysostosis associated with previously unreported neurological complaints occurred in five family members, suggesting autosomal dominant inheritance. A review of the literature is presented and previously unreported neurological complaints, e.g. neurogenic claudicatio, are emphasize

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1989.tb03196.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The results of the investigations reported here indicate that patients affected with the infantile sialic acid storage disorder (ISSD) and the original French sialuria patient suffer from distinct and fundamentally different disorders. While phase microscopy and immunochcmical studies demonstrated abnormal storage within intracellular inclusions in ISSD cells, no morphological evidence of storage within any subcellular organelles was found in the sialuria cells. Moreover, comparative subcellular fractionation studies on gradients of colloidal silica showed the excess sialic acid in ISSD cells to be located within the light (buoyant) lysosomal fraction, while the excessive, free sialic acid in the sialuria cells was found in the cytoplasmic fraction with no increased storage within the lysosomal tractions. It is concluded that the sialic acid abnormalities in ISSD and the French type of sialuria are the result of very different biochemical and genetically unrelated abnormalities.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1989.tb03197.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The point prevalence at birth of osteogenesis imperfecta was estimated by a systematic search of all children born 1.1. 1970 to 31. XII. 1983 in the county of Fyn (Denmark). Additionally, the population prevalence on 31. XII. 1983 of all patients with osteogenesis imperfecta in this county was determined. The county is a well‐defined, representative subregion of Denmark which demographically comprises a cross‐section including about 9% of the Danish population. Altogether, the study disclosed 48 patients with osteogenesis imperfecta. Of these, 17 patients were born 1.1. 1970 to 31. XII. 1983 and 12 had type I, 2 had type II, 2 had type III, and 1 had type IV. Thus, the point prevalence at birth was 21.8/‐100 000 and the population prevalence was 10.6/100 000 inhabitans. There was great variation in the clinical manifestations within and between the

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1989.tb03198.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

A family with inv8(p23q22), in which one girl with a derivative chromosome 8 showed the characteristic phenotype, is reported. Our case differs from the 32 known families with inv8(p23q22), being the first of apparently non‐Hispanic descent. The anomaly may, however, have its origins in the Spanish domination of Sicil

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1989.tb03199.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

This report presents a case of cyclopia attributable to an unbalanced karyotype in a family with a balanced, reciprocal 3/7 translocation. This case was the fifth recorded in three generations of this family. From this report it is possible that the simultaneous action of partial trisomy 3p and partial monosomy 7q may be one cause of holoprosencephaly.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1989.tb03200.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1989.tb03201.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY