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At least 37 records · Page 2Linked to original sources
PubMed1991

Insulin and glucose levels and prevalence of glucose intolerance in pedigrees with multiple diabetic siblings.

Hyperinsulinemia may be an early inherited marker for a defect in insulin action that subsequently results in glucose intolerance and non-insulin-dependent diabetes mellitus (NIDDM). To examine the role of hyperinsulinemia in individuals at high genetic risk for NIDDM and determine the prevalence of impaired glucose tolerance (IGT) and newly diagnosed diabetes in members of NIDDM pedigrees, we studied 310 members of 16 pedigrees ascertained for greater than or equal to 2 NIDDM siblings. Nondiabetic members of all pedigrees were examined by 75-g oral glucose tolerance test with fasting and 1-h insulin levels. Participants had height and weight recorded. Spouses of pedigree members (n = 88) served as control subjects. The spouse control subjects were older and slightly more obese than the undiagnosed pedigree members. The prevalence of IGT was 14.8% in spouses and 7.7% in pedigree members, and NIDDM was present in 11.3% of spouses and 2.3% of previously undiagnosed pedigree members. However, neither spouses nor pedigree members differed significantly from published age-specific prevalence rates for IGT or newly diagnosed NIDDM. Insulin and glucose levels were examined in pedigree members with normal glucose tolerance (NGT). Fasting insulin levels were not significantly different between spouses and NGT pedigree members. However, after adjustment for age, weight (body mass index), and sex, NGT pedigree members had higher 1-h insulin levels and higher fasting and 1-h glucose levels than spouses. These differences were also evident when pedigree members with at least 1 affected (NIDDM or IGT) parent were compared with spouses with no family history of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2026

Fault-tolerant pedigree reconstruction from pairwise kinship relations.

MOTIVATION: Pedigrees reconstructed from biologically related ancient genomes have revealed many insights into (pre)history. To our knowledge, all reported ancient pedigrees have been primarily manually reconstructed, as existing pedigree reconstruction methods are ill-suited for the quality and nature of ancient DNA data. RESULTS: We introduce repare, an open-source software method to automatically reconstruct pedigrees from inferred pairwise kinship relations, which are readily obtainable from ancient genomes. This method reconstructs pedigrees by iteratively incorporating pairwise kinship relations into a set of candidate pedigrees, with pruning and sampling to reduce its search space. It optionally considers supporting information such as haplogroups and skeletal age-at-death estimates. We evaluate this method on a variety of simulated pedigrees with varying error rates and missingness. We also use this method to reconstruct several published pedigrees that were originally manually reconstructed; for one, we present a potential alternative topology. repare optionally incorporates user-inferred pedigree constraints, enabling "human-in-the-loop" reconstruction workflows. Especially when used with these user-inferred constraints, we find that repare represents a powerful and flexible tool for ancient pedigree reconstruction. AVAILABILITY AND IMPLEMENTATION: repare is freely available at https://github.com/Narasimhan-Lab/repare. In addition, source code, benchmark scripts, and benchmark results used in this work are archived at https://doi.org/10.5281/zenodo.19716772.

Pedigree↗
PubMed2003

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study.

BACKGROUND: High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. RESULTS: Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. CONCLUSION: Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions.

Adult↗
PubMed1989

Identifying pedigrees segregating at a major locus for a quantitative trait: an efficient strategy for linkage analysis.

Having found evidence for segregation at a major locus for a quantitative trait, a logical next step is to identify those pedigrees in which major-locus segregation is occurring. If the quantitative trait is a risk factor for an associated disease, identifying such segregating pedigrees can be important in classifying families by etiology, in risk assessment, and in suggesting treatment modalities. Identifying segregating pedigrees can also be helpful in selecting pedigrees to include in a subsequent linkage study to map the major locus. Here, we describe a strategy to identify pedigrees segregating at a major locus for a quantitative trait. We apply this pedigree selection strategy to simulated data generated under a major-locus or mixed model with a rare dominant allele and sampled according to one of several fixed-structure or sequential sampling designs. We demonstrate that for the situations considered, the pedigree selection strategy is sensitive and specific and that a linkage study based only on the pedigrees classified as segregating extracts essentially all the linkage information in the entire sample of pedigrees. Our results suggest that for large-scale linkage studies involving many genetic markers, the savings from this strategy can be substantial and that, compared with fixed-structure sampling, sequential sampling of pedigrees can greatly improve the efficiency for linkage analysis of a quantitative trait.

Genetic Linkage↗
PubMed1995

Inherent intractability of the ascertainment problem for pedigree data: a general likelihood framework.

The problem of ascertainment in segregation analysis arises when families are selected for study through ascertainment of affected individuals. In this case, ascertainment must be corrected for in data analysis. However, methods for ascertainment correction are not available for many common sampling schemes, e.g., sequential sampling of extended pedigrees (except in the case of "single" selection). Concerns about whether ascertainment correction is even required for large pedigrees, about whether and how multiple probands in the same pedigree can be taken into account properly, and about how to apply sequential sampling strategies have occupied many investigators in recent years. We address these concerns by reconsidering a central issue, namely, how to handle pedigree structure (including size). We introduce a new distinction, between sampling in such a way that observed pedigree structure does not depend on which pedigree members are probands (proband-independent [PI] sampling) and sampling in such a way that observed pedigree structure does depend on who are the probands (proband-dependent [PD] sampling). This distinction corresponds roughly (but not exactly) to the distinction between fixed-structure and sequential sampling. We show that conditioning on observed pedigree structure in ascertained data sets obtained under PD sampling is not in general correct (with the exception of "single" selection), while PI sampling of pedigree structures larger than simple sibships is generally not possible. Yet, in practice one has little choice but to condition on observed pedigree structure. We conclude that the problem of genetic modeling in ascertained data sets is, in most situations, literally intractable. We recommend that future efforts focus on the development of robust approximate approaches to the problem.

Family Characteristics↗
PubMed1996

Maternal inheritance and chromosome 18 allele sharing in unilineal bipolar illness pedigrees.

We have replicated the observation of McMahon et al. [1995] that there is excess maternal transmission of illness in a series of previously described unilineal Bipolar manic-depressive illness extended pedigrees [Berrettini et al., 1991]. ("Transmission" is defined for any ill person in a pedigree when father or mother has a personal or immediate family history of major affective disorder.) We divided our pedigrees into exclusively maternal transmission (Mat) and mixed maternal-paternal transmission (in different pedigree branches) (Pat). Using affected sib-pair-analysis, linkage to a series of markers on chromosome 18p-cen was observed in the Pat but not the Mat pedigrees, with significantly greater identity by descent (IBD) at these markers in the Pat pedigrees. As compared with the pedigree series as a whole, the proportion of alleles IBD in the linkage region is much increased in the Pat pedigrees. As shown by Kruglyak and Lander [1995], as the sharing proportion of alleles in affected relative pairs increases, the number of such pairs needed to resolve the linkage region to a 1 cM interval becomes smaller. Genetic subdivision of an illness by clinical or pedigree configuration criteria may thus play an important role in discovery of disease susceptibility mutations.

Alleles↗
PubMed1991

Genetic variation in insulin receptor beta-chain exons among members of familial type 2 (non-insulin-dependent) diabetic pedigrees.

Insulin resistance appears to be an essential component of Type 2 (non-insulin-dependent) diabetes mellitus. Both hyperinsulinaemia and insulin resistance are inherited and may precede the onset of Type 2 diabetes. To determine whether insulin receptor gene mutations, and specifically whether mutations of the beta-chain could account for the observed insulin resistance, we studied members of 16 pedigrees ascertained for two or more Type 2 diabetic siblings and members of four additional pedigrees ascertained for a mixture of Type 1 and Type 2 diabetes. We previously demonstrated insulin resistance among unaffected members of these pedigrees. Each pedigree was initially examined with insulin receptor restriction fragment length polymorphisms to determine whether any allele segregated with Type 2 diabetes in these pedigrees. Of the 16 pedigrees ascertained for Type 2 diabetes, at least one recombinant event between diabetes and the insulin receptor locus was present in seven pedigrees. An additional two pedigrees showed no linkage if individuals with impaired glucose tolerance were also considered affected. In all but one of the remaining pedigrees, apparent sharing of haplotypes may have resulted from insufficient polymorphism to distinguish all parental alleles. Subsequently, exons 13-21 of each allele which appeared in a Type 2 diabetic individual were examined by single strand conformation polymorphisms to detect any mutations in this region. A total of five mutations were detected, but DNA sequence analysis showed each mutation to be silent and thus not likely to result in defective insulin receptor function. No mutation detected in this fashion was present on an allele which appeared to segregate with Type 2 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2000

Pedigree parables.

Pedigrees are a foundation of genetic counseling and human genetic research. To protect patient/subject and family privacy and confidentiality it is not unusual to find published pedigrees that have been masked (i.e. a pedigree that has been changed in ways that are obvious to the reader such as diamonds to mask gender) or altered (i.e. changing pedigree information in ways that are not obvious to the reader such as changing gender and birth order or deleting unaffected siblings from the pedigree). Failure to report pedigree data (e.g. omitting ages, ethnicity, etc.) is another measure used to protect subject and family confidentiality. At what point do such practices hinder the recognition of genetic processes? Is there evidence that harm has occurred to subjects who have appeared in published pedigrees? How does the researcher or clinician determine which information is essential to record on the pedigree? The author uses a historical perspective and case examples to illustrate the issues of balancing protection of the genetic subject's privacy with the reporting of unaltered family data. The author presents several critical questions for peer reviewers and investigators to consider when a pedigree is included in a manuscript, or for researchers involved in family studies.

Eugenics↗
PubMed1988

Insulin gene in familial NIDDM. Lack of linkage in Utah Mormon pedigrees.

Although non-insulin-dependent diabetes mellitus (NIDDM) is well recognized to be an inherited disease, the genetic lesion responsible remains to be determined. Several pedigrees have been reported in which defects of the insulin gene result in glucose intolerance or diabetes in affected members, but the role of insulin gene mutations in NIDDM is unknown. To evaluate this role, we ascertained 23 Caucasian pedigrees for a diabetic individual with at least one diabetic family member, sampled the unaffected individuals by a 75-g glucose tolerance test, and prepared leukocyte DNA on all family members. Included in the pedigrees ascertained were those with both predominantly lean and predominantly obese diabetic members and four pedigrees included as insulin-dependent diabetic individual. Insulin gene involvement was evaluated via previously described restriction-fragment-length polymorphisms (RFLPs) for the insulin gene and the nearby c-Ha-Ras oncogene (HRAS). Combination of these RFLPs resulted in the ability to trace the insulin alleles in all pedigrees studied. Analysis of individual pedigrees for sharing of insulin alleles was possible in 12 pedigrees, and lack of linkage was demonstrated in 6 of them. Neither linkage nor lack of linkage could be proved in the remaining pedigrees. Analysis of the pooled pedigree data failed to demonstrate linkage under several models, including autosomal-dominant and -recessive inheritance with different sporadic frequencies of diabetes and different prevalence figures. These results show that mutations of the insulin gene and the immediately surrounding area, including regulatory regions of the insulin gene, are unlikely to account for a significant subset of NIDDM in Caucasian individuals.

Diabetes Mellitus, Type 2↗
PubMed2001

[Sequence analysis of mtDNA 12S rRNA, tRNA(Leu(UUR)),tRNA(Ser(UCN))and 16S rRNA gene of 12 nonsyndromic inherited deafness pedigrees].

OBJECTIVE: To detect the relationship of mtDNA mutation with inherited deafness and the reason for pedigree's hypersensitivity to ototoxicity of aminoglycoside antibiotics(AmAn). METHODS: Pedigree investigations were conducted. The blood samples were obtained from 12 pedigrees, and DNA was extracted from the isolated leukocytes. After that, mtDNA fragments were amplified by PCR. The 1555(G), 3243(G) and 7445(G) mutations were detected by Alw 26 I, Apa I and Xba I restriction endonuclease digestion respectively, and then sequencing of 12S rRNA, tRNA(Leu(UUR)), tRNA(Ser(UCN))and 16S rRNA gene was performed. RESULTS: Restriction endonuclease digestion and sequence analysis showed that all the pedigrees carried mtDNA mutation, among them, 10 pedigrees carried 1555(G) mutation; 2 pedigrees, 7445(G) mutation; no pedigree was found to harbor the 3243(G) mutation. Sequence analysis of 16S rRNA gene showed that the mutations are 2230(G), 2230(AG), 2243(AG), 2230(AA). CONCLUSION: The pedigrees that carried 1555(G) or 7445(G) mutation showed hereditary or congenital hearing loss. The 1555(G) or 7445(G) mutation in association with 16S rRNA gene mutation led to pedigree's hypersensitivity to AmAn ototoxicity.

Base Sequence↗
PubMed1988

Hypertension and sodium-lithium countertransport in Utah pedigrees: evidence for major-locus inheritance.

Likelihood analysis was used to test for evidence that an allele at a major locus elevates rates of sodium-lithium countertransport (SLC) in a sample of 1,989 members of 89 Utah pedigrees. The pedigrees were ascertained through two or three sibs who died of stroke before age 74 years (stroke pedigrees), through hypertensive and normotensive probands of the Salt Lake Center of the Hypertension Detection and Followup Program (HDFP pedigrees), or through men who suffered a myocardial infarction before age 55 years (coronary pedigrees). Major-locus inheritance could be rejected in the total sample; transmission probability estimates of tau1 = .972, tau2 = .520, tau3 = .185 differed significantly from Mendelian transmission specified by tau1 = 1, tau2 = 1/2, tau3 = 0. However, heterogeneity between ascertainment groups was significant (chi2(18) = 40.06, P less than .01) and justified analysis within subsets of the sample. In the stroke pedigrees, evidence of major-locus inheritance was not found; polygenic heritability was estimated as .647. In the HDFP pedigrees, estimates of tau1 = .987, tau2 = .430, tau3 = .506 differed significantly from Mendelian transmission; the inferred model consisted of a mixture of two distributions incompatible with both Mendelian and environmental transmission but compatible with polygenic inheritance within distributions. In the coronary pedigrees, the hypothesis of Mendelian transmission could not be rejected. In the coronary pedigrees, the evidence supported an incompletely recessive allele with a frequency of .227 which elevated the level of SLC to a mean of .530 mmol/liter RBC/h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2005

Linkage at 5q14.3-15 in multiplex systemic lupus erythematosus pedigrees stratified by autoimmune thyroid disease.

OBJECTIVE: To identify genetic effects potentially shared between systemic lupus erythematosus (SLE) and autoimmune thyroiditis (AITD). METHODS: Families from the Lupus Multiplex Registry and Repository were studied in which there was at least 1 member who had both SLE and AITD (Graves' disease or Hashimoto thyroiditis). Genome scan genotyping findings in these pedigrees were evaluated for evidence of genetic linkage, by the maximum-likelihood parametric method. Nineteen pedigrees were used in the initial genome scan. Subsequently, an independent sample of 16 pedigrees was used to replicate findings. RESULTS: Studies of the first set of 19 pedigrees yielded a 2-point parametric logarithm of odds (LOD) of 4.97, which was independently confirmed in the replication sample of 16 pedigrees (LOD 2.89). For all 35 pedigrees together, the 2-point LOD was 7.86, under a dominant model used for screening with 90% penetrance and a disease allele frequency of 10%. The multipoint locus homogeneity LOD in the 35 pedigrees was 6.90 (alpha = 1.0) at 5q14.3-15 between D5S1725 and D5S1453, a 12-cM interval, with the peak at D5S1462 at 96.64 cM (nonparametric linkage P = 0.00002). Fine mapping further confirmed the genetic linkage effect and narrowed the region likely to contain the gene to approximately 5 Mb. CONCLUSION: These results suggest that stratifying SLE pedigrees by the presence of other autoimmune disorders may facilitate the discovery of genes related to SLE and that 5q14.3-15 harbors a susceptibility gene shared by SLE and AITD.

Chromosomes, Human, Pair 5↗
PubMed2006

A comparison of several methods for haplotype frequency estimation and haplotype reconstruction for tightly linked markers from general pedigrees.

Haplotype inference for tightly linked markers from general pedigrees remains a challenging problem. Only a few methods are available to efficiently and accurately estimate haplotype frequencies and reconstruct haplotypes for a large number of tightly linked markers from general pedigrees in the presence of missing data, and their performance has not been carefully and extensively evaluated. In this paper, we compare four published methods for haplotype reconstruction and frequency estimation for tightly linked markers from general pedigrees, including HAPLORE, GENEHUNTER, PedPhase, and MERLIN. We review these methods and discuss the differences between them in terms of the models and computational strategies employed. We assess their performance based on simulations using pedigrees and haplotypes on tightly linked single nucleotide polymorphisms from real studies. We investigate the effect of several factors, including the missing rate, the departure from Hardy-Weinberg Equilibrium, and the sample size, on the accuracy for haplotype inference. We also compare these methods with a widely used method for haplotype inference from unrelated individuals, PHASE, by treating individuals within a pedigree as unrelated samples. This comparison allows us to investigate the relative efficiency in haplotype inference using pedigree data. Our results indicate that incorporation of pedigree information can improve the precision for haplotype frequency estimation and the accuracy for haplotype reconstruction. Among four haplotyping methods capable of analyzing general pedigrees, HAPLORE and MERLIN have comparable performance and outperform the other two methods in almost all situations.

Computer Simulation↗
PubMed2006

Estimating the power of variance component linkage analysis in large pedigrees.

Variance component linkage analysis is commonly used to map quantitative trait loci (QTLs) in general pedigrees. Large pedigrees are especially attractive for these studies because they provide greater power per genotyped individual than small pedigrees. We propose accurate and computationally efficient methods to calculate the analytical power of variance component linkage analysis that can accommodate large pedigrees. Our analytical power computation involves the approximation of the noncentrality parameter for the likelihood-ratio test by its Taylor expansions. We develop efficient algorithms to compute the second and third moments of the identical by descent (IBD) sharing distribution and enable rapid computation of the Taylor expansions. Our algorithms take advantage of natural symmetries in pedigrees and can accurately analyze many large pedigrees in a few seconds. We verify the accuracy of our power calculation via simulation in pedigrees with 2-5 generations and 2-8 siblings per sibship. We apply this proposed analytical power calculation to 98 quantitative traits in a cohort study of 6,148 Sardinians in which the largest pedigree includes 625 phenotyped individuals. Simulations based on eight representative traits show that the difference between our analytical estimation of the expected LOD score and the average of simulated LOD scores is less than 0.05 (1.5%). Although our analytical calculations are for a fully informative marker locus, in the settings we examined power was similar to what could be attained with a single nucleotide polymorphism (SNP) mapping panel (with >1 SNP/cM). Our algorithms for power analysis together with polygenic analysis are implemented in a freely available computer program, POLY.

Chromosome Mapping↗
PubMed2005

Reconstructing pedigrees: a combinatorial perspective.

A pedigree is a directed graph that displays the relationship between individuals according to their parentage. We derive a combinatorial result that shows how any pedigree-up to individuals who have no extant (present-day) ancestors-can be reconstructed from (sex-labelled) pedigrees that describe the ancestry of single extant individuals and pairs of extant individuals. Furthermore, this reconstruction can be done in polynomial time. We also provide an example to show that the corresponding reconstruction result does not hold for pedigrees that are not sex-labelled. We then show how any pedigree can also be reconstructed from two functions that just describe certain circuits in the pedigree. Finally, we obtain an enumeration result for pedigrees that is relevant to the question of how many segregating sites are needed to reconstruct pedigrees.

Animals↗
PubMed1999

Negative symptoms of familial schizophrenia breed true in unstable (vs. stable) cerebral-ventricle pedigrees.

A pattern of negative symptoms associated with a high rate of ongoing brain and ventricular instability has been described in a cohort of schizophrenia spectrum probands (patients with schizophrenia, schizoaffective disorder depressed and bipolar, and psychosis NOS) (Garver, D.L., Nair, T.R., Christensen, J.D., Holcomb, J., Ramberg, J., Kingsbury, S., 1999. Differential patterns of premorbid functioning, symptoms and neuroleptic response in stable and unstable ventricular-volume schizophrenia. Neuropsychopharmacology 20, in press). The present study contrasts the prevalence of negative symptoms in first- and second-degree relatives of probands with unstable ventricle volume (UnsVV) and stable ventricle volume (SVV). One hundred and sixteen first- and second-degree relatives of 10 probands were interviewed using the SANS, the 'Characterization of Course: "Pattern of Symptoms"' [from Comprehensive Assessment of Symptoms and History (CASH)], SCID and SCID-II by interviewers blind to the status of the proband. Thirty-five of the 116 family members met DSM-IV criteria for schizophrenia, SA depressed, 'Cluster A' of the SCID-II (paranoid, schizotypal, schizoid personality disorder), psychosis NOS, or psychotic affective disorder. These 35 family members were defined as falling within a 'schizophrenia spectrum' as described by Farmer, A.E., McGuffin, P., Gottesman, I.I., 1987. Arch. Gen. Psychiatry 44, 634-641, but with the addition of DSM-IV affective psychosis. On that basis, the 35 members were considered 'affected family members' (AFMs). The remaining 81 family members were considered unaffected. The 'predominant symptoms of illness' (during the past 2-3 years) for 25 of the 35 AFMs could be characterized according to the 'Patterns of Symptoms' derived from the CASH. Twenty-five of the 35 AFMs were found to maintain a predominant symptom pattern during the course of illness, which could be characterized according to the 'Pattern of Symptoms' as 'predominantly positive' or 'predominantly negative'. Three of the probands had UnsVV; seven had SVV. Of the 35 AFMs, 11 were related to the UnsVV probands, and 24 were relatives of the SVV probands. The nine rated AFMs of the UnsVV probands showed a trend toward higher SANS scores (7.3 +/- 5.1) (mean +/- s.d.) than the 20 rated AFMs of SVV probands (4.3 +/- 5.1) (p = 0.08) at the time of the interview. Eighty-three per cent (eight of 10) of rated affected pedigree members of the pedigrees delineated by probands with UnsVV probands had a predominantly negative symptom course of illness, and 96% (23 of 24) of rated affected pedigree members of the pedigrees with SVV probands had a predominantly positive symptom course of illness during the preceding 2-3 years (p = 0.002). None of the 12 rated affected pedigree members within pedigrees having UnsVV probands were married at the time of the interview; 45% (14 of 31) of affected pedigree members having SVV probands were married (p = 0.004). A psychiatric disorder, characterized by unstable cerebral ventricles and predominant negative symptoms (including avoidance/failure of marital relationships) appears symptomatically to breed true in pedigrees containing schizophrenia-like illnesses.

Adult↗
PubMed2005

Pedigree construction and disease confirmation: a pilot study in Wales exploring the role of nonclinical personnel.

Pedigree construction and disease confirmation are the means by which reported family histories are translated into a verified clinical tool informing risk assessment and management decisions by clinical genetics staff. In this study, we hypothesised that pedigree generation data processes do not generally require the clinical expertise of genetic counsellors and that they could be successfully transferred to nonclinical data administrators. We made a pragmatic comparison of two processes of pedigree generation by different personnel from 14 consecutive family history questionnaires containing 88 living and decease affected individuals. The pedigrees generated by the genetic counsellor and the data administrator were compared; discrepancies were quantified and their source determined. The information gathered by the data administrator mirrored that of the genetic counsellors in 89% of cases. Time was saved by permitting direct access to cancer registry and local oncology centre databases. Constructing a pedigree is not always a case of transferring clear-cut data. Decisions need to be made about which cancers to confirm. Notable differences emerged in the number of pieces of information not transferred. Ambiguous information was often interpreted differently, suggesting the need for clinical staff to review pedigrees after their initial plotting by the data administrator. This study demonstrates a good degree of concordance between pedigrees constructed by a nonclinical data administrator and those of experienced genetic counsellors. However, the redirection of all pedigree activity to nonclinical personnel up to the point of risk review is not possible at present.

Genetic Counseling↗
PubMed2002

Genome-wide multipoint linkage analyses of multiplex schizophrenia pedigrees from the oceanic nation of Palau.

The oceanic nation of Palau has been geographically and culturally isolated over most of its 2000 year history. As part of a study of the genetic basis of schizophrenia in Palau, we genotyped five large, multigenerational schizophrenia pedigrees using markers every 10 cM (CHLC/Weber screening set 6). The number of affected/unaffected individuals genotyped per family ranged from 11/21 to 5/5. Thus the pedigrees varied in their information for linkage, but each was capable of producing a substantial LOD score. We fitted a simple dominant and recessive model to these data using multipoint linkage analysis implemented by Simwalk2. Predictably, the most informative pedigrees produced the best linkage results. After genotyping additional markers in the region, one pedigree produced a LOD = 3.4 (5q distal) under the dominant model. Seven of nine schizophrenics in the pedigree, mostly 3rd-4th degree relatives, share a 15-cM, 7-marker haplotype. For a different pedigree, another promising signal occurred on distal 3q, LOD = 2.6, for the recessive model. For two other pedigrees, the best LODs were modest, slightly better than 2.0 on 5q and 9p, while the fifth pedigree produced no noteworthy linkage signal. Similar to the results for other populations, our results suggest there are multiple genes conferring liability to schizophrenia even in the small population of Palau (roughly 21,000 individuals) in remote Oceania.

Genome, Human↗