Biomedical subjects

R C Griffiths

Publications and source records attributed to R C Griffiths.

36 records · Page 2Linked to original sources

PubMed1995

Unrooted genealogical tree probabilities in the infinitely-many-sites model.

The infinitely-many-sites process is often used to model the sequence variability observed in samples of DNA sequences. Despite its popularity, the sampling theory of the process is rather poorly understood. We describe the tree structure underlying the model and show how this may be used to compute the probability of a sample of sequences. We show how to produce the unrooted genealogy from a set of sites in which the ancestral labeling is unknown and from this the corresponding rooted genealogies. We derive recursions for the probability of the configuration of sequences (equivalently, of trees) in both the rooted and unrooted cases. We give a computational method based on Monte Carlo recursion that provides approximates to sampling probabilities for samples of any size. Among several applications, this algorithm may be used to find maximum likelihood estimators of the substitution rate, both when the ancestral labeling of sites is known and when it is unknown.

Biological Evolution↗

PubMed1994

Sampling theory for neutral alleles in a varying environment.

We develop a sampling theory for genes sampled from a population evolving with deterministically varying size. We use a coalescent approach to provide recursions for the probabilities of particular sample configurations, and describe a Monte Carlo method by which the solutions to such recursions can be approximated. We focus on infinite-alleles, infinite-sites and finite-sites models. This approach may be used to find maximum likelihood estimates of parameters of genetic interest, and to test hypotheses about the varying environment. The methods are illustrated with data from the mitochondrial control region sampled from a North American Indian tribe.

Alleles↗

PubMed1994

Determinants of forearm mineral density and its correlation with fracture history in women.

In order to evaluate the role of single photon absorptiometry (SPA) in the prediction of osteoporotic fracture risk, 1935 women, referred for measurement of forearm mineral density (FMD) at the distal radial site, were studied by questionnaire in a cross-sectional design. There was no significant decline in FMD until the age of 47, after which there was a linear decline with age of about 1.2% per year. There was no relationship between age and FMD, or forearm mineral content (FMC), in premenopausal women. There was a fall in FMD with the number of years since menopause, after correcting for the effects of age, of approximately 0.5% per year. Body weight was positively correlated with FMC in postmenopausal women. The duration of exposure to hormone replacement therapy (HRT) was positively correlated with FMD, and the magnitude of this effect was reduced the longer the delay between the onset of the menopause and the commencement of HRT. There was no significant association of FMD with calcium intake, weight-bearing exercise, tobacco or alcohol consumption, or family history of osteoporosis. FMD was significantly lower in postmenopausal women who reported fractures after the age of 25, after correcting for age and years postmenopause. In conclusion, a low FMD is predictive of a past history of fractures and may therefore be capable of predicting future fracture risk.

Absorptiometry, Photon↗

PubMed1993

The coalescent in two colonies with symmetric migration.

Kingman's coalescent process is extended to two colonies with symmetric migration. The mean waiting time until a sample of genes taken from two colonies coalesces to a common ancestor is obtained. The final step in the waiting time before the process is absorbed at 1 is observed to have an intriguing behaviour. The distribution of this final waiting time converges to the known distribution of the corresponding waiting time in the case of a single population as the migration rate tends to zero. The mean, however, does not converge. The waiting time until a sample has two common ancestors is modeled as a function of the migration rate. Finally bounds for the expected waiting time for the two colonies to have j > l ancestors are derived.

Genetics, Population↗

PubMed1993

The effects of surgery and acute rejection on glomerular hemodynamics in the transplanted rat kidney.

The effects of surgery and acute rejection on glomerular hemodynamics in the transplanted rat kidney are examined. Kidneys were transplanted from Munich-Wistar (MW) rats to syngeneic controls and MHC-incompatible PVG strain recipients. We report on 4 groups of animals: (1) two-kidney control MW rats; (2) unilaterally nephrectomized MW rats (UNX); (3) renal transplantation from MHC-identical MW littermates and removal of native kidneys (SYN); and (4) transplantation from MW donors to MHC-incompatible PVG rats and removal of native kidneys (ALLO). Glomerular filtration rate (GFR), single-nephron (SN)GFR, and glomerular capillary pressure (PGC) in SYN kidneys were depressed as compared to those in UNX (GFR, 1.41 +/- 0.08 vs. 0.80 +/- 0.08 ml/min; SNGFR, 67.2 +/- 4.8 vs. 44.7 +/- 6.6 nl/min; and PGC, 67 +/- 2 vs. 48 +/- 4 mmHg, UNX vs. SYN, respectively, P < 0.05). GFR and SNGFR in ALLO kidneys, however, were depressed even further (GFR, 0.40 +/- 0.05 ml/min; SNGFR, 13.8 +/- 1.8 nl/min; P < 0.05 for UNX vs. ALLO and SYN vs. ALLO). Afferent arteriolar resistance (RA) was increased greater than 4-fold (UNX, 1.01 +/- 0.15 10(10) dyn.sec.cm-5; SYN, 1.37 +/- 0.36 10(10) dyn.sec.cm-5; ALLO, 4.76 +/- 0.74 10(10) dyn.sec.cm-5 [P < 0.05, UNX vs. ALLO and SYN vs. ALLO]). This led to a precipitous fall in initial capillary flow rate in ALLO rats. These studies reveal the presence of moderate reductions in SNGFR and PGC in the nonrejecting transplanted kidney, which may relate to as yet unidentified consequences of the transplant surgery. More significantly, the principal mechanism leading to the reduced GFR characteristic of acute allograft rejection is identified as severe preglomerular vasoconstriction.

Acute Disease↗

PubMed1992

Statistical analysis of in situ hybridization data: derivation and use of the zmax test.

There are many situations in which grain distributions resulting from in situ hybridization of radioactively labeled probes to unique genes should be subjected to a statistical analysis. However, the problems posed by analysis of in situ hybridization data are not straightforward, and no completely satisfying method is currently available. We have developed a procedure in which the major and any number of minor site(s) of hybridization may be specifically located and the significance of each tested. This zmax procedure first tests the overall distribution for departure from randomness and then identifies significantly overlabeled whole chromosomes (or chromosome arms or other large segments), a process that may be repeated to pinpoint significantly overlabeled regions within these chromosomes. We describe in detail the derivation of the zmax statistic, present tables of significant zmax levels, and show with examples how zmax is used in tests of significance of in situ hybridization data.

Animals↗

PubMed1991

Which locus has the oldest allele?

This paper studies aspects of the distribution of non-mutant ancestors of a sample of gametes in a two-locus infinitely-many-alleles model. The ancestral process of two gametes is considered in detail. Included are algorithms for calculating the probability that the oldest allele is from the first locus, and the expected age of the oldest allele. Extensions to an r-locus model in the cases of complete linkage and independence are also studied.

Alleles↗

PubMed1991

Two chromosomes with multigene families.

Watterson's formulae for the distribution, mean, and variance of the number of alleles in common on two chromosomes with multigene families are derived as simpler forms, and extended to chromosomes with an infinite number of genes, each evolving as in an infinitely many alleles model.

Alleles↗

PubMed1990

The number of alleles in multigene families.

The probability distribution and moments of the number of alleles present in a sample of homologous chromosomes are studied. It is assumed that there are multiple copies of the gene on each chromosome. When there are only two copies per chromosome or when there are only two or three chromosomes, it is possible to use analytic methods to tackle the problem. Otherwise, a simulation method is suggested.

Alleles↗

PubMed1989

Genealogical-tree probabilities in the infinitely-many-site model.

This paper considers the distribution of the genealogical tree of a sample of genes in the infinitely-many-site model where the relative age ordering of the mutations (nodes in the tree) is known. A computer implementation of a recursion for the probability of such trees is discussed when the nodes are age-labeled, or not.

Alleles↗

PubMed1987

Counting genealogical trees.

A class of genealogical trees is related to unlabelled graph-theoretical trees, allowing some counting problems involved with genealogical trees to be solved.

Biometry↗

PubMed1983

Allele frequencies with genic selection.

The structure of the limit point process of the ordered allele frequencies in the stationary distribution of a K-allele diffusion model with mutation and genic selection is studied. This leads to a formula for expectations of functions of the allele frequencies in terms of expectations in the neutral infinite alleles model.

Alleles↗

PubMed1983

Simulating allele frequencies in a population and the genetic differentiation of populations under mutation pressure.

A method is developed for simulating the allele frequencies in an equilibrium or transient population under the effects of neutral mutation and random drift. The method is based on diffusion theory and is fast so that it can be used to study in detail the distribution of heterozygosity or any quantity that can be expressed as a function of allele frequencies. It has been applied to study the distribution of heterozygosity and the distribution of the frequencies of the first three most frequent alleles in a population. It also has been applied to study the distribution of the number of alleles shared by two populations that were derived from a common stock.

Alleles↗

PubMed1980