Type Of Pedigree Research Articles

Joint Linkage and Association Analysis Using GENEHUNTER-MODSCORE with an Application to Familial Pancreatic Cancer

Introduction: Joint linkage and association (JLA) analysis combines two disease gene mapping strategies: linkage information contained in families and association information contained in populations. Such a JLA analysis can increase mapping power, especially when the evidence for both linkage and association is low to moderate. Similarly, an association analysis based on haplotypes instead of single markers can increase mapping power when the association pattern is complex. Methods: In this paper, we present an extension to the GENEHUNTER-MODSCORE software package that enables a JLA analysis based on haplotypes and uses information from arbitrary pedigree types and unrelated individuals. Our new JLA method is an extension of the MOD score approach for linkage analysis, which allows the estimation of trait-model and linkage disequilibrium (LD) parameters, i.e., penetrance, disease-allele frequency, and haplotype frequencies. LD is modeled between alleles at a single diallelic disease locus and up to three diallelic test markers. Linkage information is contributed by additional multi-allelic flanking markers. We investigated the statistical properties of our JLA implementation using extensive simulations, and we compared our approach to another commonly used single-marker JLA test. To demonstrate the applicability of our new method in practice, we analyzed pedigree data from the German National Case Collection for Familial Pancreatic Cancer (FaPaCa). Results: Based on the simulated data, we demonstrated the validity of our JLA-MOD score analysis implementation and identified scenarios in which haplotype-based tests outperformed the single-marker test. The estimated trait-model and LD parameters were in good accordance with the simulated values. Our method outperformed another commonly used JLA single-marker test when the LD pattern was complex. The exploratory analysis of the FaPaCa families led to the identification of a promising genetic region on chromosome 22q13.33, which can serve as a starting point for future mutation analysis and molecular research in pancreatic cancer. Conclusion: Our newly proposed JLA-MOD score method proves to be a valuable gene mapping and characterization tool, especially when either linkage or association information alone provide insufficient power to identify the disease-causing genetic variants.

Resulting of pedigree and topology of centripetal spatial schema in Chinese traditional cities

Chinese Traditional Maps and Local Chronicles serve as significant sources for investigating the urban history of ancient Chinese cities. These documents prioritize the abstract representation of topological relationships over precise numerical values and geometric shapes. This is consistent with the traditional Chinese city image and spatial schema emphasizing “harmony between man and nature”. Most Chinese Traditional Maps reflect a centripetal spatial schema, wherein the core area is located at the center, and other locations are positioned hierarchically about the center. Based on this data, this research aims to categorize and examine the development and evolution of the centripetal spatial schema in ancient Chinese cities by constructing a pedigree of types. The authors identify three types and summarize their causes, calculate the topological features, and reveal their correlations with the type of pedigree. This study reveals that cities with different centripetal forms exhibit regular differences in the accessibility, centrality, and functional attributes of central nodes, as well as the proportion of nodes with different attributes in the city. Overall, the conclusion aims to deepen people's understanding of traditional Chinese spatial concepts at the macro-urban level, particularly in the context of China's current urban renewal wave. Additionally, it provides practical references for inheriting and applying Chinese traditional construction wisdom.

The Spatial Pedigree in Traditional Villages under the Perspective of Urban Regeneration—Taking 728 Villages in Jiangnan Region, China as Cases

In current urban regeneration, the conservation and reuse of traditional village space are significant measures to activate urban-rural development. Traditional villages in the Jiangnan region of eastern China represent the typical vernacular culture of urban-rural settlements, which affects the dynamic development of urban regeneration. Aiming at the disadvantages of the decentralization of research objects and the simplification of spatial characteristics in the research of traditional villages in the Jiangnan region, this paper will construct the spatial pedigrees of villages. This study takes 728 traditional villages in the Jiangnan region as cases. First, through on-site research, the spatial pattern of villages in isolated areas was mapped and drawn. Then, on the basis of on-site review, this study labeled the village space, summarized village space information, and used ArcGIS and BIM to create a 3D model of the village. In ArcGIS platform through SOA to establish criterion framework for recognizing the types of village pedigree. Finally, the classification of villages was spatially visualized, and a pedigree was constructed according to the type context. The research result indicates: (1) The aggregation mode of traditional villages in the south of the Jiangnan region presents the characteristics of local aggregation and partial dispersion, which are directly affected by factors such as elevation, water system, and road system. (2) Analysis of the spatial pedigrees of traditional villages through spatial types and spatial growth patterns revealed four pedigree types, including spatial environment pedigree, the spatial organization pedigree, spatial morphological pedigree, and architectural form pedigree. (3) The pedigree shows and distinguishes independent developmental context and evolved form, presenting an extended pattern of prototypes and sub-types.

Effect of familial clustering in the genetic screening of 235 French ALS families

ObjectivesTo determine whether the familial clustering of amyotrophic lateral sclerosis (ALS) cases and the phenotype of the disease may help identify the pathogenic genes involved.MethodsWe conducted a targeted next-generation sequencing...

Meat productivity and interior features of the different genotypes of the rams Edilbaev breed

One of the key factors ensuring the increase in sheep production in future is the development of intensive reproduction of the herd. The article presents the results of an experiment that helped study and give comparative characteristics for the meat productivity and natural resistance of the pedigree Edilbay sheep breed in conditions of a pedigree reproducer in 2018-2019. The young stocks of original and new types were studied to assess their interior traits, establish the direction and degree of correlation between the biochemical blood parameters and meat productivity of young sheep, as well as determine indices reflecting the immune status of organisms of the experimental sheep. When starting the test, the live weight of animals of the pure and pedigree types were almost the same, while when finishing the experiment at the age of 12 months, animals in Group II exceeded animals in Group I by 4.3 kg (5.8%, P<0.01). The best average daily gain of experimental sheep was also in Group II, i.e., 167 g, which was higher than in Group I by 9.1% (P<0.01). Consequently, the rams of new type had the highest growth rate. The data of the control slaughter showed that both experimental groups had high meat productivity. The analysis of natural resistance indicators of small ruminants of various types and their relationship with productive qualities in different climatic zones have also shown the need to use different integral indicators to assess the immune status in further breeding of animals. The analysis of natural resistance indicators of small ruminants of various types and their relation with productive qualities in different climatic zones has suggested that there is a need to use several markers to assess the immune status for further sheep breeding.

Risk of Prostate Cancer Associated With Familial and Hereditary Cancer Syndromes.

Recently developed clinical guidelines suggest that men in families with specific cancer syndromes, such as hereditary breast and ovarian cancer (HBOC), consider genetic testing, especially in the setting of aggressive disease. However, although a family history (FH) of the same disease among close relatives is an established risk factor for prostate cancer (PC), a direct comparison of PC risk for men with each syndrome in a single population is needed. The Utah Population Database was used to identify 619,630 men, age ≥ 40 years, who were members of a pedigree that included at least 3 consecutive generations. Each man was evaluated for FH of hereditary PC (HPC), HBOC, and Lynch syndrome (LS) and for his own PC status. PC occurrences (N = 36,360) were classified into one or more subtypes: early onset (EO), lethal, and/or clinically significant. Relative risks (RRs) associated with each subtype, adjusted for important covariables, were calculated in STATA using a modified Poisson regression with robust error variances to obtain corresponding RR CIs for each FH definition. An FH of HPC conveyed the greatest relative risk for all PC subtypes combined (RR, 2.30; 95% CI, 2.22 to 2.40), followed by HBOC and LS (both with 1 < RR < 2 and statistically significant). The strongest risks associated with FH were observed for EO disease in all pedigree types, consistent with the contribution of genetic factors to disease occurrence. In this large, population-based, family database, the risk of PC varied by cancer FH and was most strongly associated with EO disease. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance.

BREEDING VALUE ASSESSMENT OF VARIOUS INBREED TYPES OF VLADIMIR DRAFT HORSES

Vladimir draft horse belongs to the group of breeds with limited gene pool and threatening status, since the total number of mares in the breed is no more than 200 heads. Vladimir breed horses are distinguished by endurance, ambitiousness, beauty and harmonious forms, good mobility and meet all modern requirements of a draft horse. The limited number of livestock and t distribution area leads to the use of inbreeding, which affects the quality of horses. Nowadays, two original inbreeding types have formed in the breed, characterized by typological features: Yuryev-Polsky and Gavrilovo-Posadsky. The aim of our work was to evaluate the breeding qualities of Vladimir draft horses of various internal breeds, to determine the best lines andfamilies for further breeding and increase the number of breeds. As a result of the research, a change in the number of horse stocks over the past 40 years was analyzed; differences in the development of the main parameters and body type of these inbred types during evolution were established. A qualitative analysis of the breeding value of pedigree types is carried out. For this purpose, the typicality of horses, the exterior and the constitution according to the point system were evaluated. The main body indices (format, mass and bones) were calculated, and a differential assessment of tallness and bones was carried out. Evaluation of Vladimir breed mares by categories of breeding value showed that the largest number of horses of the 1st class was in Yuryev-Polsky inbreed type.

Underestimation and misclassification of mutations at X chromosome STRs depend on population’s allelic profile

Short tandem repeats are extremely abundant in the human genome and widely used in population and forensic genetics. The conventional approach to estimate mutation rates for STRs involves the detection of Mendelian incompatibilities and their frequency quantification, in family duos or trios. In this work, we aim to measure the impact this estimation methodology implies in the underestimation of mutation rates.We computed two independent experiences simulating one single-step mutation and one double step mutation in each pedigree. The pedigree with the highest number of compatibilities observed (hidden mutations) was mother-daughter duo, followed by the father-daughter duo, mother-son duo and, finally, mother-father-child trio, for the one and two-steps simulations. The estimation of X-STRs mutation rates from simple counting proved to be biased through systematic underestimation in an extent which depends on allele frequencies distribution of the marker, type of pedigree and number of repeat units involved.

Heritability of blood pressure traits in diverse populations: a systematic review and meta-analysis.

To understand the genetic architecture and make inferences about transmissible resemblance of systolic and diastolic blood pressure (SBP and DBP) traits in relatives, the polygenic effect of individual alleles in terms of narrow heritability (h2) is usually assessed. The heritability estimates for BP traits are population specific parameters with a wide range in different studies (6-68%), and there is no comprehensive evidence comparing its source(s) of heterogeneity. To fill the gap, this systematic review and meta-analysis study was carried out. Using MeSH terms, 647 records were detected through searching, "Pubmed," "Ebsco," "Web of Science," and "Scopus" databases. From these, 24 relevant full-text articles with 47 comparisons for final quantitative meta-analysis were included in our review over the five continents. The additive genetic effects of both traits showed a widespread distribution (h2SBP: 17-52%, h2DBP:19-41%). Different categories of transmissible resemblance for BP traits were explained by ethnicity; higher heritability was estimated in Europeans and Mexican Americans, while lower heritability was seen in the Middle Eastern, Asians, Africans, Latinos, Hispanics, and American Indians. Low heterogeneity of polygenic effects was seen for both traits in subgroups of the Middle East, Asians, Africans, and Latinos, Hispanics, American Indians. However, there was a substantial heterogeneity of h2 within European and Mexican American studies. Neither pedigree type nor other covariates explained the variance of additive genetic effects of BP traits in different ethnicities.

A Family-Based Rare Haplotype Association Method for Quantitative Traits

Background: The variants identified in genome-wide association studies account for only a small fraction of disease heritability. A key to this “missing heritability” is believed to be rare variants. Specifically, we focus on rare haplotype variant (rHTV). The existing methods for detecting rHTV are mostly population-based, and as such, are susceptible to population stratification and admixture, leading to an inflated false-positive rate. Family-based methods are more robust in this respect. Methods: We propose a method for detecting rHTVs associated with quantitative traits called family-based quantitative Bayesian LASSO (famQBL). FamQBL can analyze any type of pedigree and is based on a mixed model framework. We regularize the haplotype effects using Bayesian LASSO and estimate the posterior distributions using Markov chain Monte Carlo methods. Results: We conduct simulation studies, including analyses of Genetic Analysis Workshop 18 simulated data, to study the properties of famQBL and compare with a standard family-based haplotype association test implemented in FBAT (family-based association test) software. We find famQBL to be more powerful than FBAT with well-controlled false-positive rates. We also apply famQBL to the Framingham Heart Study data and detect an rHTV associated with diastolic blood pressure. Conclusion: FamQBL can help uncover rHTVs associated with quantitative traits.

Estimation of Trait-Model Parameters in a MOD Score Linkage Analysis

Background/Aims: Theoretically, the trait-model parameters (disease allele frequency and penetrance function) can be estimated without bias in a MOD score linkage analysis. We aimed to practically evaluate the MOD score approach regarding its ability to provide unbiased trait-model parameters for various pedigree-type and trait-model scenarios. We further investigated the ability of the MOD score approach to detect imprinting using affected sib pairs (ASPs) and affected half-sib pairs (AHSPs) when all parental genotypes are missing. Methods: Simulated pedigree data were analyzed using the GENEHUNTER-MODSCORE software package. Parameter estimation performance in terms of bias and variability was evaluated with regard to trait-model type and pedigree complexity. Results: Generally, parameters were estimated with lower bias and variability with increasing pedigree complexity, especially for recessive and overdominant models. However, dominant and additive models could hardly be distinguished even when using 3-generation pedigrees. Imprinting could clearly be detected for mixtures of mainly ASPs and only few AHSPs with the common parent of the imprinted sex, even though no parental genotypes were available. Conclusion: Our results provide guidance to researchers regarding the possibility to estimate trait-model parameters by a MOD score analysis, including the degree of imprinting, with certain types of pedigrees.

GenomeLaser: fast and accurate haplotyping from pedigree genotypes.

We present a software tool called GenomeLaser that determines the haplotypes of each person from unphased high-throughput genotypes in family pedigrees. This method features high accuracy, chromosome-range phasing distance, linear computing, flexible pedigree types and flexible genetic marker types. http://www.4dgenome.com/software/genomelaser.html.

Enetic diversity in red clover (Trifolium pratense L.) using SSR markers

Red clover (Trifolium pratense L.) is one of the main forage species from temperate regions and it's originated in Eurasia where wild-type populations are found in the Caucasus Mountains. Considerable variation for this crop has been recorded for few molecular variations. The identification and understanding of molecular genetic diversity in red clover accessions will help in effective genetic conservation along with efficient breeding programs in this crop. This study has shown molecular diversity using microsatellite markers in red clover accessions from around of the world. In this investigation, 40 genotypes have been selected and analyzed using 15 SSR primers. These primer pairs amplified 1146 polymorphic loci among the genotypes screened. The number of fragments amplified by each SSR primer combination varied from 24 for RCS3681 to 109 for RCS1729 with an average value of 80.78 per primer combination. The SSR marker data was further analyzed using cluster algorithms and Principal coordinates analysis (PCoA). The results indicated that the considerable genetic variations were discovered among the analyzed genotypes. The SSR based clustering could identify the putative pedigree types of the present red clover types of diverse origins.

Combining results of forensic STR kits: HDplex validation including allelic association and linkage testing with NGM and Identifiler loci

The autosomal short tandem repeat (STR) kits that are currently used in forensic science have a high discrimination power. However, this discrimination power is sometimes not sufficient for complex kinship analyses or decreases when alleles are missing due to degradation of the DNA. The Investigator HDplex kit contains nine STRs that are additional to the commonly used forensic markers, and we validated this kit to assist human identification. With the increasing number of markers it becomes inevitable that forensic and kinship analyses include two or more STRs present on the same chromosome. To examine whether such markers can be regarded as independent, we evaluated the 30 STRs present in NGM, Identifiler and HDplex. Among these 30 markers, 17 syntenic STR pairs can be formed. Allelic association between these pairs was examined using 335 Dutch reference samples and no linkage disequilibrium was detected, which makes it possible to use the product rule for profile probability calculations in unrelated individuals. Linkage between syntenic STRs was studied by determining the recombination fraction between them in five three-generation CEPH families. The recombination fractions were compared to the physical and genetic distances between the markers. For most types of pedigrees, the kinship analyses can be performed using the product rule, and for those cases that require an alternative calculation method (Gill et al., Forensic Sci Int Genet 6:477-486, 2011), the recombination fractions as determined in this study can be used. Finally, we calculated the (combined) match probabilities, for the supplementary genotyping results of HDplex, NGM and Identifiler.

Risk factors for death from canine parvoviral-related disease in Australia

Canine parvovirus (CPV) is a highly contagious cause of serious and often fatal disease in dogs worldwide despite the availability of safe and efficacious vaccines. Although a number of studies have focussed on identifying risk factors in disease development, risk factors associated with death from CPV are largely unknown. In this study we analysed a total of 1451 CPV cases reported from an Australian surveillance system – using univariate and multivariate techniques – to determine significant risk factors associated with death and euthanasia. A crude case fatality rate of 42.3% was estimated – higher than has been reported previously. We found that 3.3% of CPV cases had a history of vaccination in the previous 12 months, despite having completed the primary puppy vaccination course. The majority (89.5%) of these cases occurred in dogs <12 months of age, indicating failure of the primary vaccination course to provide protective immunity (most likely due to interference of the vaccine antigen with maternal antibodies but other reasons are discussed). Extending the age at which the final puppy vaccination is administered might be one of several strategies to consider. The final multivariate model showed that in non-litter CPV cases, risk of death was significantly associated with season of diagnosis (summer) and pedigree type (hounds and non-sporting dogs). Euthanasia in non-litter CPV cases was significantly associated with season of diagnosis (summer), state of residence (Northern Territory/South Australia/Tasmania combined), age (<six months) and vaccination status (unvaccinated and unknown). No significant risk factors associated with death were identified in cases in which there was more than one puppy in a litter infected. The risk factors identified in this study can be used as prognostic indicators for veterinarians faced with CPV cases. The possible explanations for the associations identified and their clinical relevance to CPV case outcome are discussed

Detection of innocent systolic murmurs by auscultation and their relation to hematologic and echocardiographic findings in clinically normal Whippets

To determine murmur prevalence by auscultation of 105 apparently healthy Whippets without signs of cardiac disease, to determine the origin of these murmurs, and to evaluate the influence of sex, type of pedigree (ie, bred for showing or racing), and training on these murmurs. Cross-sectional study. 105 client-owned Whippets. All dogs were auscultated by the first author and underwent a complete physical and cardiological examination, together with a hematologic assessment. Several RBC variables and echocardiographic variables were compared between dogs with or without a murmur at the level of the aortic valve. 44 of 105 (41.9%) dogs had no murmur. A soft systolic murmur was present with point of maximal intensity at the level of the aortic valve in 50 (47.6%) dogs, at the level of the pulmonic valve in 8 (7.6%) dogs, and at the level of the mitral valve in 3 (2.9%) dogs. No significant differences were found in heart rate, rhythm, murmur presence, point of maximal intensity, and murmur grade between males and females, between dogs with race- and show-type pedigrees, or between dogs in training and not in training. Dogs with a murmur at the level of the aortic valve had a significantly higher aortic and pulmonic blood flow velocity and cardiac output, compared with dogs without a murmur. Whippets have a high prevalence of soft systolic murmurs in the absence of any structural abnormalities, which fit the description of innocent murmurs. No influence of sex, pedigree type, or training was found on the occurrence of these murmurs in Whippets.

225 EFFECTS OF PEDIGREE, MEAT QUALITY, AND MEAT QUANTITY OF SLAUGHTERHOUSE DONOR COWS ON OOCYTE RECOVERY, EMBRYO DEVELOPMENT, AND PREGNANCY AFTER EMBRYO TRANSFER

In conventional in vitro embryo production, oocytes are obtained from various ovaries, and donor characteristics, such as pedigree type, meat quality, or meat quantity, are not considered. The aim of this study was to examine the effects of pedigree type and meat quality and quantity of slaughterhouse donor cows on oocyte recovery, embryo development, and pregnancy rates. The ovaries of individual Korean native cows were obtained from a slaughterhouse. The ear tag numbers were obtained 24 h after slaughter, and the donor data were compared according to the pedigree type (no registration to third bloodline registration), meat quantity according to the percentage of carcass weight (more than 69%, 66 to 69%, and below 66%; Grades A, B, and C, respectively), and meat quality according to the marbling grade (marbling grade 8 to 9, 6 to 7, 4 to 5, 2 to 3, and 1; Grades 1++, 1+, 1, 2, and 3, respectively). There were 390 donors in total, and each group had 30 donors. Recipients (Holstein heifers; n = 222) were synchronized with a progesterone device, and a single blastocyst was transferred nonsurgically on Day 7 from the onset of oestrus. Data on embryo development were compared by Duncan’s multiple range tests, and pregnancy rate was analysed by chi-square test. Values of P &lt; 0.05 were considered to indicate a significant difference. No significant difference was detected in the average number of oocytes recovered (17.5 ± 2.9 to 22.9 ± 1.2%) or blastocyst development (16.4 ± 2.6 to 19.5 ± 3.4%) from cows of different pedigrees. A higher number of oocytes were recovered from Grade A (22.9 ± 1.0) than from Grade B (19.8 ± 0.7; P &lt; 0.05) cows. However, the meat quantity grade had no significant effect on blastocyst development (14.3 ± 1.2 to 15.0 ± 0.8%). A greater number of oocytes were recovered from the Grade 1++ (25.0 ± 1.6), 1+ (27.7 ± 2.4), and 2 (23.6 ± 1.5) groups than from the Grade 3 group (19.7 ± 1.0; P &lt; 0.05). The developmental rate to the blastocyst stage was significantly higher in the Grades 2 and 3 groups (22.1 ± 2.2 and 19.4 ± 1.7) than in the Grade 1++, 1+, and 1 groups (9.0 ± 1.2 to 13.8 ± 2.0). Pregnancy rate was not affected by pedigree type, meat quantity, or meat quality (41.7 to 58.6%). We concluded that 1) pedigree type had no effect on oocyte recovery and embryo development; 2) meat quantity affected oocyte recovery but did not affect embryo development; 3) high meat quality (Grades 1++ and 1+) resulted in greater oocyte recovery but lower embryo development; and 4) pregnancy rate remained unaffected by pedigree type, meat quantity, and meat quality. This research was supported by the Technology Development Program for Agriculture and Forestry, Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea.

High prevalence of epilepsy in a village in the Littoral Province of Cameroon

In the Littoral Province of Cameroon, in the Sanaga River Valley, a door-to-door epidemiological study was carried out in order to evaluate the prevalence of epilepsy in a small village located in a geographically isolated area, hyper-endemic for onchocerciasis. It was followed by an electro-clinical evaluation of patients and a case-control study. The study involved a three-phases design: in phase I, a screening questionnaire was administered, in phase II, the presence of epilepsy was confirmed with electro-clinical evaluation, and in phase III, risk factors for epilepsy, socio-economical factors and life habits were evaluated in patients and two matched controls for the age (+/-1 year) residents in the same village. Endemicity level of onchocerciasis was assessed in the village by measuring the prevalence of nodules in adult males aged >or=20 years (PNAM). One hundred eighty-one subjects (100 male and 81 female) were examined (91.9% of the overall population). The crude prevalence rate of active epilepsy was 105 per 1000 pop (CI 95% 60-150) while the age-adjusted prevalence rate was 134.5 cases per 1000 pop (CI 95% 90-178). Seizures were classified as generalized in 10 patients (52.6%) and partial in nine (47.4%). In 17 patients EEG was recorded. Afterward the electro-clinical classification this distribution was inverted: generalized seizures occurred in 35.3% of cases and partial seizures in 64.7% of cases. The PNAM was 62.5%. The surveyed village was classified as hyper-endemic for onchocerciasis. Among risk factors, only positive family history for epilepsy was found (p=0.031). A sample pedigree of a family with 10 epileptic cases (4 included in the epidemiological study) was showed. To our knowledge, this is the first door-to-door study that produce an adjusted prevalence rate on epilepsy in Cameroon. In according to studies done in Tanzania, Liberia, Uganda, and Ethiopia, our results (i.e., the high prevalence rate in a restricted area, the clinical characteristics of epileptic seizures, the positive family history for epilepsy and the type of pedigree of a family with epileptic patients) may be accounted for by the presence of an strong interaction between environmental and genetic factors in some circumscribed areas.

Chemical Biology at Berkeley

C hemical Biology has transformed the curriculum and student composition of the Department of Chemistry at the University of California, Berkeley (UC Berkeley). The rapid growth in this area has been fueled by the steadily increasing number of young scientists who seek to apply chemical reasoning, synthetic techniques, and quantitative analysis to the study of biomolecules and the cellular contexts in which they reside. To a significant extent, these interests have been inspired by the growth of the biotechnology industry, and over the years several members of Berkeley’s Chemistry Advisory Board have suggested that individuals with both chemical and biological experience will be in increasing demand. As further evidence for this need, many Bay Area companies have been providing generous financial backing to support these interdisciplinary training efforts in our department. Equally important has been the growth of chemical biology research throughout the academic community, which has offered an expanded set of opportunities for advanced study and future academic employment for students who emerge with this type of pedigree. As the popularity of this scientific area grew, however, it quickly became clear that new programswould be needed to train students broadly in chemistry and biologywithout compromising scientific rigor. To answer this call, UC Berkeley has integrated new training opportunities and instructional approaches into both the graduate and undergraduate chemistry curricula. What has emerged is a vibrant chemical biology community that has invigorated the Berkeley Chemistry Program and initiated numerous collaborations among a diverse set of research groups. The Berkeley Chemical Biology Graduate Program. This effort began with the development of a Chemical Biology Graduate Program (CBGP), which was designed to expand the set of research opportunities that are available for students with these interdisciplinary interests. The participants are selected from the graduate admissions pools of four departments: molecular and cell biology (MCB); chemistry; chemical engineering; and bioengineering. At this time the current students are from MCB and chemistry. The CBGP does not offer a degree in chemical biology but is designed to enhance the program of the student’s home department. Students from MCB, for example, meet both the requirements of CBGP and of MCB. Students in chemistry who join the CBGP still take their Ph.D. qualifying exams in the sameway as other chemistry students. A key aspect of this program has been the incorporation of research rotations for all participants. Througha series of three10week rotations, the CBGP students gain hands-on experience that can solidify their ideas about the type of research that is personally the most rewarding. The students are strongly encouraged to explore a broad set of options before ultimately selecting a thesis laboratory for the remainder of their stay at Berkeley. As a result of this opportunity, many students have selected a laboratory that they might not have even considered under other circumstances. In 2001, a pilot rotation program began for three students in the Chemistry Graduate Program. The department covered a sig*Corresponding author, francis@cchem.berkeley.edu.

Interpretation of simultaneous linkage and family‐based association tests in genome screens

Linkage and association analyses have played important roles in identifying susceptibility genes for complex diseases. Linkage tests and family-based tests of association are often applied in the same data to help fine-map disease loci or validate results. This paradigm increases efficiency by making maximal use of family data sets. However, it is not intuitively clear under what conditions association and linkage tests performed in the same data set may be correlated. Understanding this relationship is important for interpreting the combined results of both tests. We used computer simulations and theoretical statements to estimate the correlation between linkage statistics (affected sib pair maximum LOD scores) and family-based association statistics (pedigree disequilibrium test (PDT) and association in the pressure of linkage (APL)) under various hypotheses. Different types of pedigrees were studied: nuclear families with affected sib pairs, extended pedigrees and incomplete pedigrees. Both simulation and theoretical results showed that when there is no linkage or no association, the linkage and association tests are not correlated. When there is linkage and association in the data, the two tests have a positive correlation. We concluded that when linkage and association tests are applied in the same data, the type I error rate of neither test will be affected and that power can be increased by applying tests conditionally.