Biomedical subjects

D C Shields

Publications and source records attributed to D C Shields.

77 records · Page 5Linked to original sources

PubMed1988

"Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons.

The patterns of synonymous codon usage in 91 Drosophila melanogaster genes have been examined. Codon usage varies strikingly among genes. This variation is associated with differences in G+C content at silent sites, but (unlike the situation in mammalian genes) these differences are not correlated with variation in intron base composition and so are not easily explicable in terms of mutational biases. Instead, those genes with high G+C content at silent sites, resulting from a strong "preference" for a particular subset of the codons that are mostly C-ending, appear to be the more highly expressed genes. This suggests that G+C content is reduced in sequences where selective constraints are weaker, as indeed seen in a pseudogene. These and other data discussed are consistent with the effects of translational selection among synonymous codons, as seen in unicellular organisms. The existence of selective constraints on silent substitutions, which may vary in strength among genes, has implications for the use of silent molecular clocks.

Animals↗

PubMed1987

Synonymous codon usage in Bacillus subtilis reflects both translational selection and mutational biases.

Codon usage data for 56 Bacillus subtilis genes show that synonymous codon usage in B. subtilis is less biased than in Escherichia coli, or in Saccharomyces cerevisiae. Nevertheless, certain genes with a high codon bias can be identified by correspondence analysis, and also by various indices of codon bias. These genes are very highly expressed, and a general trend (a decrease) in codon bias across genes seems to correspond to decreasing expression level. This, then, may be a general phenomenon in unicellular organisms. The unusually small effect of translational selection on the pattern of codon usage in lowly expressed genes in B. subtilis yields similar dinucleotide frequencies among different codon positions, and on complementary strands. These patterns could arise through selection on DNA structure, but more probably are largely determined by mutation. This prevalence of mutational bias could lead to difficulties in assessing whether open reading frames encode proteins.

Bacillus subtilis↗

PubMedDate not supplied

Complex segregation analysis of thyroid autoantibodies: are they inherited as an autosomal dominant trait?

The presence of circulating autoantibodies (Abs) to the thyroid antigens thyroid peroxidase (TPO) and thyroglobulin (Tg) is a marker for autoimmune thyroid disease. Recent studies have suggested that the tendency to produce these Abs is inherited as an autosomal dominant characteristic. In order to confirm or refute these observations, we have carried out a complex segregation analysis using POINTER on Ab data in 86 unselected pedigrees (172 nuclear families). The overall prevalence of TPO Ab was 9.9% in men and 24.1% in women. Tg Ab was found in 11.0% of men and 23.5% of women. There was a marked tendency for both TPO Ab and Tg Ab to cluster in families and complex segregation analysis provided strong evidence for vertical transmission. However, it was not possible to distinguish between a single locus and a multifactorial model for either Ab. In the absence of strong evidence for a single locus, genetic linkage strategies are unlikely to be successful.

Adolescent↗

PubMedDate not supplied

Prediction of genetic risks from segregation analyses of morbid risks.

Segregation analysis provides a genetic model of disease based upon morbid risks in age-specific classes, from which the model derives genotype-specific morbid risks. In the absence of disease-specific mortality each morbid risk is a cumulative incidence (age-specific penetrance). If disease-specific mortality reduces the number of affected in the older classes, the morbid risk is less than the corresponding penetrance. When counselling individuals with a family history of disease, their genetic risk is a function of penetrances, which can be calculated from morbid risks. We have applied this method to breast, ovarian and colorectal cancer.

Genetic Diseases, Inborn↗

PubMedDate not supplied

Segregation analysis of colorectal cancer in Northern Ireland.

The genetic basis for colorectal cancer was investigated by complex segregation analysis of a published series of 305 pedigrees ascertained through a large population database. Two hundred and five of the pedigrees were ascertained through patients diagnosed with colorectal cancer before age 55, and 100 from patients diagnosed with colorectal cancer between the ages of 55 and 74. The analysis was carried out using the program POINTER. Using the joint-likelihood approach, the familial aggregation of colorectal cancer was compatible with the inheritance of a dominant gene. The gene frequency of the putative abnormal allele was 0.002 with a lifetime penetrance of 85%. However, under conditional likelihood, this mode of inheritance for a major gene was not favoured. The possible aetiologies of this paradoxical finding are discussed.

Adult↗