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PubMed2004

A genome scan for diabetic nephropathy in African Americans.

BACKGROUND: There is substantial evidence for a genetic contribution to diabetic nephropathy susceptibility in the African American population, but little is known about location or identity of susceptibility genes. METHODS: DNA samples were collected from 206 type 2 diabetes (T2DM) and end-stage renal disease (ESRD)/nephropathy-affected sib pairs from 166 African American families (355 affected individuals). A genome scan was performed and data analyzed using nonparametric linkage regression (NPLR) analysis and ordered subsets analysis (OSA) methods. RESULTS: In initial NPLR analyses no logarithm of odds (LOD) scores >2.0 were observed. Four loci had LOD scores > or =1.0, with LOD = 1.43 at 29 cM on chromosome 7p the highest. NPLR analyses of multilocus interactions detected 6 loci (7p, 12p, 14q, 16p, 18q, and 21q) with LOD scores 1.15 to 1.63. NPLR analyses evaluating phenotypic interactions revealed multiple locations with evidence (P < 0.05) for interactions with age-at-onset of ESRD (9 loci), duration of diabetes before onset of ESRD (19 loci), and age-at-onset of diabetes (14 loci). Several loci identified by NPLR analyses were also identified using OSA. OSA revealed evidence for a nephropathy locus at 135 cM on chromosome 3 in an estimated 29% of the families (LOD = 4.55 in the optimal subset). Additional linkage evidence, LOD = 3.59, was observed on chromosome 7p (37% of the families, longer duration of diabetes prior to diagnosis of ESRD), and 18q (max. LOD = 3.72; 64% of the families, early diabetes diagnosis). The 7p linkage has been observed in a recent genome scan of African American type 2 diabetes. CONCLUSION: This first genome scan of diabetic nephropathy in African Americans reveals evidence for susceptibility loci on chromosomes 3q, 7p, and 18q. The 7p locus may represent a type 2 diabetes susceptibility locus.

Adult↗
PubMed1995

How can maximum likelihood methods reveal candidate gene effects on a quantitative trait?

Different maximum likelihood approaches were used to explore the role of candidate genes in the variability of quantitative trait Q1 while accounting for the effects of age, Q2, and Q3. Segregation analysis, under the class D regressive model, provides evidence for a Mendelian gene effect on the adjusted trait Q1. Results of gene mapping through lod-score analyses remain puzzling. Pairwise lod scores indicate a possible linkage with the candidate gene C5 which is excluded when using tightly linked informative marker loci. Finally, our combined segregation and linkage analysis clearly shows that a C5 linked gene is involved in Q1 variability. However, given the lod-score results within the C5 region, we postulate a more complex mechanism for Q1 than a single di-allelic C5 linked gene. The knowledge of the true model (C5 is MG1 and has three alleles) permits a partial explanation of our results. This study demonstrates the advantages of using complementary approaches to reveal the role of candidate genes in complex traits, and the value of simultaneous estimation of linkage and segregation parameters.

Alleles↗
PubMed2006

Phenotypic definition of Chiari type I malformation coupled with high-density SNP genome screen shows significant evidence for linkage to regions on chromosomes 9 and 15.

Chiari type I malformation (CMI; OMIM 118420) is narrowly defined when the tonsils of the cerebellum extend below the foramen magnum, leading to a variety of neurological symptoms. It is widely thought that a small posterior fossa (PF) volume, relative to the total cranial volume leads to a cramped cerebellum and herniation of the tonsils into the top of the spinal column. In a collection of magnetic resonance imagings (MRIs) from affected individuals and their family members, we measured correlations between ten cranial morphologies and estimated their heritability in these families. Correlations between bones delineating the PF and significant heritability of PF volume (0.955, P = 0.003) support the cramped PF theory and a genetic basis for this condition. In a collection of 23 families with 71 affected individuals, we performed a genome wide linkage screen of over 10,000 SNPs across the genome to identify regions of linkage to CMI. Two-point LOD scores on chromosome 15 reached 3.3 and multipoint scores in this region identified a 13 cM region with LOD scores over 1 (15q21.1-22.3). This region contains a biologically plausible gene for CMI, fibrillin-1, which is a major gene in Marfan syndrome and has been linked to Shprintzen-Goldberg syndrome, of which CMI is a distinguishing characteristic. Multipoint LOD scores on chromosome 9 maximized at 3.05, identifying a 40 cM region with LOD scores over 1 (9q21.33-33.1) and a tighter region with multipoint LOD scores over 2 that was only 8.5 cM. This linkage evidence supports a genetic role in Chiari malformation and justifies further exploration with fine mapping and investigation of candidate genes in these regions.

Arnold-Chiari Malformation↗
PubMed2002

Application of AFLP markers for QTL mapping in the rabbit.

Two rabbit (Oryctolagus cuniculus) inbred strains (AX/JU and IIIVO/JU) have been used for genetic analysis of quantitative traits related to dietary cholesterol susceptibility. Application of the AFLP (amplified fragment length polymorphism) technique with 15 primer combinations revealed 226 polymorphisms between the 2 inbred strains. A total of 57 animals from a backcross progeny (IIIVO/JU x [IIIVO/JU x AX/JU]F1) were available for the genetic analysis. These backcross animals were fed a commercial pelleted diet fortified with 0.3% w/w cholesterol during a test period that lasted five weeks. A male genetic map could be constructed, consisting of 12 linkage groups and 103 AFLP markers. Linkage analysis between the cholesterol-related traits and marker loci revealed a significant LOD score for the relative weight of adrenal glands in males (LOD score = 3.83), whereas suggestive linkages were found for basal serum total cholesterol levels in females (LOD score = 2.69), for serum total cholesterol response (area under the curve) in males (LOD score = 2.21), and for hematocrit in males (LOD score = 3.24).

Adrenal Glands↗
PubMed1996

Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23.

Manic depressive illness, or bipolar disorder (BP), is characterized by episodes of elevated mood (mania) and depression. We designed a multistage study in the genetically isolated population of the Central Valley of Costa Rica to identify genes that promote susceptibility to severe BP (termed BPI), and screened the genome ot two Costa Rican BPI pedigrees (McInnes et al., submitted). We considered only individuals who fulfilled very stringent diagnostic criteria for BPI to be affected. The strongest evidence for a BPI locus was observed in 18q22-q23. We tested 16 additional markers in this region and seven yielded peak lod scores over 1.0. These suggestive lod scores were obtained over a far greater chromosomal length (about 40 cM) than in any other genome region. This localization is supported by marker haplotypes shared by 23 of 26 BPI affected individuals studied. Additionally, marker allele frequencies over portions of this region are significantly different in the patient sample from those of the general Costa Rican population. Finally, we performed an analysis which made use of both the evidence for linkage and for association in 18q23, and we observed significant lod scores for two markers in this region.

Alleles↗
PubMed2000

Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis.

A major determinant of the risk for osteoporosis is peak bone mineral density (BMD), which is largely determined by genetic factors. We recently reported linkage of peak BMD in a large sample of healthy sister pairs to chromosome 11q12-13. To identify additional loci underlying normal variations in peak BMD, we conducted an autosomal genome screen in 429 Caucasian sister pairs. Multipoint LOD scores were computed for BMD at four skeletal sites. Chromosomal regions with LOD scores above 1.85 were further pursued in an expanded sample of 595 sister pairs (464 Caucasians and 131 African-Americans). The highest LOD score attained in the expanded sample was 3.86 at chromosome 1q21-23 with lumbar spine BMD. Chromosome 5q33-35 gave a LOD score of 2.23 with femoral neck BMD. At chromosome 6p11-12, the 464 Caucasian pairs achieved a LOD score of 2.13 with lumbar spine BMD. Markers within the 11q12-13 region continued to support linkage to femoral neck BMD, although the peak LOD score was decreased to 2.16 in the sample of 595 sibling pairs. Our study is the largest genome screen to date for genes underlying variations in peak BMD and represents an important step toward identifying genes contributing to osteoporosis in the general population.

Adult↗
PubMed1999

Linkage of familial schizophrenia to chromosome 13q32.

Over the past 4 years, a number of investigators have reported findings suggestive of linkage to schizophrenia, with markers on chromosomes 13q32 and 8p21, with one recent study by Blouin et al. reporting significant linkage to these regions. As part of an ongoing genome scan, we evaluated microsatellite markers spanning chromosomes 8 and 13, for linkage to schizophrenia, in 21 extended Canadian families. Families were analyzed under autosomal dominant and recessive models, with broad and narrow definitions of schizophrenia. All models produced positive LOD scores with markers on 13q, with higher scores under the recessive models. The maximum three-point LOD scores were obtained under the recessive-broad model: 3.92 at recombination fraction (theta).1 with D13S793, under homogeneity, and 4.42 with alpha=.65 and straight theta=0 with D13S793, under heterogeneity. Positive LOD scores were also obtained, under all models, for markers on 8p. Although a maximum two-point LOD score of 3.49 was obtained under the dominant-narrow model with D8S136 at straight theta=0.1, multipoint analysis with closely flanking markers reduced the maximum LOD score in this region to 2. 13. These results provide independent significant evidence of linkage of a schizophrenia-susceptibility locus to markers on 13q32 and support the presence of a second susceptibility locus on 8p21.

Canada↗
PubMed2005

Fine mapping of a major locus on chromosome 10 for exploratory and fear-like behavior in mice.

Advanced intercross lines (AIL) and interval-specific congenic strains (ISCS) were used to fine map previously coarsely defined quantitative trait loci (QTL) on Chromosomes 1, 10, and 19, influencing behaviors in the open Field (OF) and light-dark (LD) paradigms in mice. F12(A x B) AIL mice (N = 1130) were phenotyped, genotyped, and mapped. The ISCS were studied only in the telomeric Chromosome 10 region of interest, containing the exploratory and excitability QTL1 (Exq1). The Chromosome 10 Exq1 and Chromosome 19 Exq4 loci mapped robustly in the AIL. The most significant QTL findings (2.0 LOD score intervals; peak; LOD score) came from the TD15 and LD transitions traits, yielding estimated intervals of 2.2 cM for Exq1 (71.3-73.5 cM; peak 72.3 cM; LOD 11.9) and 9.0 cM for Exq4 (29.0-38.2 cM; peak 34 cM; LOD 4.2). The replicated QTLs on Chromosome 1 failed to map in this AIL population. The ISCS data confirmed Exq1 loci in general. However, the ISCS data were complex and less definitive for localizing the Exq1 loci. These exploratory and fear-like behaviors result from inheriting "many small things," namely, QTL explaining 2%-7% of the phenotypic variance. These results highlight the challenges of positionally cloning loci of small effect for complex traits. In particular, fine-mapping success may depend on the genetic architecture underlying complex traits.

Animals↗
PubMed2004

Comparison of microsatellites versus single-nucleotide polymorphisms in a genome linkage screen for prostate cancer-susceptibility Loci.

Prostate cancer is one of the most common cancers among men and has long been recognized to occur in familial clusters. Brothers and sons of affected men have a 2-3-fold increased risk of developing prostate cancer. However, identification of genetic susceptibility loci for prostate cancer has been extremely difficult. Although the suggestion of linkage has been reported for many chromosomes, the most promising regions have been difficult to replicate. In this study, we compare genome linkage scans using microsatellites with those using single-nucleotide polymorphisms (SNPs), performed in 467 men with prostate cancer from 167 families. For the microsatellites, the ABI Prism Linkage Mapping Set version 2, with 402 microsatellite markers, was used, and, for the SNPs, the Early Access Affymetrix Mapping 10K array was used. Our results show that the presence of linkage disequilibrium (LD) among SNPs can lead to inflated LOD scores, and this seems to be an artifact due to the assumption of linkage equilibrium that is required by the current genetic-linkage software. After excluding SNPs with high LD, we found a number of new LOD-score peaks with values of at least 2.0 that were not found by the microsatellite markers: chromosome 8, with a maximum model-free LOD score of 2.2; chromosome 2, with a LOD score of 2.1; chromosome 6, with a LOD score of 4.2; and chromosome 12, with a LOD score of 3.9. The LOD scores for chromosomes 6 and 12 are difficult to interpret, because they occurred only at the extreme ends of the chromosomes. The greatest gain provided by the SNP markers was a large increase in the linkage information content, with an average information content of 61% for the SNPs, versus an average of 41% for the microsatellite markers. The strengths and weaknesses of microsatellite versus SNP markers are illustrated by the results of our genome linkage scans.

Chromosome Mapping↗
PubMed2004

A genome scan for joint-specific hand osteoarthritis susceptibility: The Framingham Study.

OBJECTIVE: Studies investigating hand osteoarthritis (OA) as a single entity have not shown strong linkage of the disease with any chromosomal sites. We undertook this study to test our hypothesis that phenotypes of hand OA may show stronger linkage than has been shown for overall hand OA. METHODS: We performed a factor analysis on measures of hand OA to determine patterns of disease. Using the joint regions identified by this analysis, we performed a genome-wide linkage analysis for OA susceptibility loci using 426 original cohort members and 790 offspring cohort members in 267 pedigrees. Radiographic OA features evaluated included the Kellgren/Lawrence score, osteophytes, and joint space narrowing. Prior to linkage analysis, standardized residuals were computed from regression analysis of each phenotype on age. This was performed separately for each sex and cohort. The variance component model (GeneHunter) was then applied to the normalized scores of the residuals of both sexes and cohorts. RESULTS: There was evidence suggestive of linkage (logarithm of odds [LOD] score >1.5) at 16 sites. Four of these sites had LOD scores >3.0. Two of these sites (identified in the full sample) included a linkage region for OA of the distal interphalangeal (DIP) joint on chromosome 7 (155 cM; LOD score 3.06) and a linkage region for OA of the first carpometacarpal (CMC) joint on chromosome 15 (81 cM; LOD score 6.25). The other 2 sites (identified in women) included a linkage region for OA of the DIP joint on chromosome 1 (202 cM; LOD score 3.03) and a linkage region for OA of the first CMC joint on chromosome 20 (4 cM; LOD score 3.74). CONCLUSION: These data suggest that several chromosomes contain hand OA susceptibility genes and that a joint-specific approach may be more rewarding than a global approach to the genetics of hand OA. Further investigation of these regions is warranted using finer maps and other populations.

Chromosome Mapping↗
PubMed1994

A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3.

In a preliminary genome scan of 47 bipolar disorder families, we detected in one family a lod score of 3.41 at the PFKL locus on chromosome 21q22.3. The lod score is robust to marker allele frequencies, phenocopy rates and age-dependent penetrance, and remains strongly positive with changes in affection status. Fourteen other markers in 21q22.3 were tested on this family, with largely positive lod scores. Five of the other 46 families also show positive, but modest lod scores with PFKL. When all 47 families are analysed together, there is little support for linkage to PFKL under homogeneity or heterogeneity using lod score analysis, but the model-free affected-pedigree-member method yields statistically significant results (p < 0.0003). Our results are consistent with the presence of a gene in 21q22.3 predisposing at least one family to bipolar disorder.

Adolescent↗
PubMed2004

A quantitative trait locus influences coordinated variation in measures of ApoB-containing lipoproteins.

Lipoprotein phenotypes are known to be strongly intercorrelated. These intercorrelations are due to genetic and environmental effects on common metabolic pathways. The purpose of this study was to determine if we could localize genes that exert pleiotropic effects on multiple related lipoprotein traits in humans. Using data from the San Antonio Family Heart Study, we extracted principal components from a set of 12 intercorrelated lipoprotein traits that included phenotypes reflecting lipid and protein concentrations and size distributions for LDLs and HDLs. Five principal components were extracted from the data and all were significantly heritable (h(2) = 0.41-0.57). When subjected to linkage analyses, only one, Component 5, returned a LOD score > or = 3 (LOD score was 3.0 at 38cM on chromosome 15; genome-wide P-value = 0.039). LDL median diameter (-0.529), non-HDLC (-0.422), and ApoB (-0.403) concentrations were the only traits with loadings (absolute value) >0.4, suggesting Component 5 is related to LDL size or perhaps more generally to beta-lipoprotein metabolism. Surprisingly, none of the 12 original lipoprotein traits had a LOD >1 in this region of chromosome 15. These data provide evidence for a novel gene, influencing beta-lipoprotein phenotypes, whose effect(s) is detected only when several lipoprotein traits are considered together.

Adult↗
PubMed2004

Genome-wide linkage analyses for age at diagnosis of hypertension and early-onset hypertension in the HyperGEN study.

A genome-wide scan was performed to identify chromosomal regions related to age at diagnosis of hypertension and to early-onset hypertension in white and African American families from the Hypertension Genetic Epidemiology Network (HyperGEN). Age at diagnosis of hypertension was reported by participants at recruitment and standardized residuals adjusted for sex, study center, and body mass index were created. Participants were classified as having early-onset hypertension if their reported age at diagnosis was before 45 years in whites or before 35 years in African Americans. Variance component linkage analysis was performed for age at diagnosis and an affected sibpair linkage analysis was performed for early-onset hypertension, both implemented in GENEHUNTER. In whites, the heritability of diagnosis age was estimated to be 35% and the maximum LOD score was found on chromosome 1 at 123 cM (LOD = 1.48). The maximum LOD score for early-onset hypertension was located on chromosome 18 at 69 cM (LOD = 1.21). In African Americans, the heritability of age of diagnosis was estimated to be 42% and the maximum LOD scores were found on chromosome 4 at 120 cM (LOD = 2.44) and on chromosome 15 at 60 cM (LOD = 2.31). The maximum LOD for early-onset hypertension in African Americans was also on chromosome 4 at 153 cM (LOD = 2.05) and overlies the mineralocorticoid receptor. Although these results report modest LOD scores, several of these loci have been previously reported to be linked to hypertension and blood pressure, lending further support that genes related to the risk of hypertension may be at these loci.

Adult↗
PubMed1997

Suggestive evidence for linkage of schizophrenia to markers on chromosome 13 in Caucasian but not Oriental populations.

Previously we reported suggestive evidence for linkage of schizophrenia to markers on chromosome 13q14.1-q32. We have now studied an additional independent sample of 44 pedigrees consisting of 34 Taiwanese, 9 English and 1 Welsh family in an attempt to replicate this finding. Narrow and broad models based on Research Diagnostic Criteria or the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, were used to define the schizophrenia phenotype. Under a dominant genetic model, two-point lod scores obtained for most of the markers were negative except that marker D13S122 gave a total lod score of 1.06 (theta = 0.2, broad model). As combining pedigrees from different ethnic origins may be inappropriate, we combined this replication sample and our original sample, and then divided the total sample into Caucasian (English and Welsh pedigrees) and Oriental (Taiwanese and Japanese pedigrees) groups. The Caucasian pedigrees produced maximized admixture two-point lod scores (A-lod) of 1.41 for the marker D13S119 (theta = 0.2, alpha = 1.0) and 1.54 for D13S128 (theta = 0, alpha = 0.3) with nearby markers also producing positive A-lod scores. When five-point model-free linkage analysis was applied to the Caucasian sample, a maximum lod score of 2.58 was obtained around the markers D13S122 and D13S128, which are located on chromosome 13q32. The linkage results for the Oriental group were less positive than the Caucasian group. Our results again suggest that there is a potential susceptibility locus for schizophrenia on chromosome 13q14.1-q32, especially in the Caucasian population.

Asian People↗
PubMedDate not supplied

Nomenclature guidelines for X-linked mental retardation.

Nomenclature guidelines are proposed for non-specific and for syndromal forms of X-linked mental retardation. Non-specific mental retardations (MRX) are given unique symbols for each family (MRX1, MRX2, MRX3 ...). Syndromal mental retardations (MRXS) which do not as yet have specific symbols are given unique interim symbols for each syndrome (MRXS1, MRXS2, MRXS3 ...). The prerequisite for assignment of serial MRX and MRXS gene symbols is a minimum lod score (or multipoint lod score) of +2 between the MR locus and one or more X chromosome markers. Prior approval of availability for proposed gene symbols must be obtained from the Nomenclature Committee of the Human Gene Mapping Workshops.

Chromosome Mapping↗
PubMed1990

RFLP analysis of three different types of acute intermittent porphyria.

Restriction fragment length polymorphism (RFLP) analysis was performed in three Finnish families with different subtypes of acute intermittent porphyria (AIP): 1) cross-reacting immunological material (CRIM)-negative with low erythrocyte porphobilinogen (PBG)-deaminase activity, 2) CRIM-positive with low PBG-deaminase activity and 3) CRIM-negative with normal PBG-deaminase activity. The disease-associated RFLP haplotype (A2B1C2) of the PBG-deaminase gene was the same in each family. In all three families, RFLP linkage analysis resulted in highly positive lod scores. The maximal lod score (4.3) was obtained at the recombinant fraction of zero, thus confirming a tight linkage of AIP to the PBG-deaminase locus. Of the 62 family members tested, 30 had the disease-associated haplotype; in 5 of them, conventional tests for AIP were normal and in one, uncertain. RFLP analysis can thus reveal new gene carriers and help in the diagnosis of individuals with uncertain results in other laboratory tests.

Acute Disease↗
PubMed2002

The significance of distal bronchial samples with commensals in ventilator-associated pneumonia: colonizer or pathogen?

STUDY OBJECTIVE: To investigate the role of oropharyngeal and cutaneous commensal microorganisms (OCCs) as a cause of ventilator-associated pneumonia (VAP). DESIGN: Retrospective analysis of the medical and microbiological records. SETTING: One medical-surgical ICU. PATIENTS: All VAP episodes recorded during a 10-year period were reviewed. All patients with suspected VAP underwent bronchoscopy with protected-specimen brush (PSB) sampling and BAL before any change in antibiotic therapy was made. OCC-VAP was defined as VAP with significant growth in quantitative cultures (PSB yielded > or = 10(3) cfu/mL and/or BAL yielded > or = 10(4) cfu/mL) of OCCs only. Three experts reviewed the episodes. Exposed patients (ie, those with OCC-VAP) and unexposed patients (ie, patients without VAP) matched on condition severity at ICU admission and mechanical ventilation duration were compared. RESULTS: Twenty-nine episodes in 28 patients with > or = 10(4) cfu/mL OCCs in BAL fluid and/or > or = 10(3) cfu/mL OCCs in PSB specimens were found. All patients in these episodes had new radiologic lung infiltrates, with 26 episodes involving purulent tracheal aspirates, 23 episodes involving temperatures > or = 38.5 degrees C, and 18 episodes involving > or = 11,000 leukocytes/ microL. The main OCCs found were non-beta-hemolytic Streptococcus spp (n = 12), Neisseria spp (n = 7), and coagulase-negative Staphylococcus spp (n = 6). Other possible reasons for fever and the presence of new chest infiltrates were found in 20 and 17 patients, respectively. Histologic evidence of pneumonia was found in 2 of the 10 patients who died. The three experts agreed on the diagnosis for 23 patients. In the OCC-VAP group only, the mean (+/- SD) logistic organ dysfunction (LOD) scores increased significantly (LOD score, 2 +/- 4; p = 0.008) during the 3 days before bronchoscopy, and ICU stay duration was longer than in the unexposed group. The exposed/unexposed study found no difference in mortality. CONCLUSION: OCCs may behave like classic nosocomial pathogens in critically ill patients.

Adult↗
PubMed2002

A genomewide scan identifies two novel loci involved in specific language impairment.

Approximately 4% of English-speaking children are affected by specific language impairment (SLI), a disorder in the development of language skills despite adequate opportunity and normal intelligence. Several studies have indicated the importance of genetic factors in SLI; a positive family history confers an increased risk of development, and concordance in monozygotic twins consistently exceeds that in dizygotic twins. However, like many behavioral traits, SLI is assumed to be genetically complex, with several loci contributing to the overall risk. We have compiled 98 families drawn from epidemiological and clinical populations, all with probands whose standard language scores fall > or =1.5 SD below the mean for their age. Systematic genomewide quantitative-trait-locus analysis of three language-related measures (i.e., the Clinical Evaluation of Language Fundamentals-Revised [CELF-R] receptive and expressive scales and the nonword repetition [NWR] test) yielded two regions, one on chromosome 16 and one on 19, that both had maximum LOD scores of 3.55. Simulations suggest that, of these two multipoint results, the NWR linkage to chromosome 16q is the most significant, with empirical P values reaching 10(-5), under both Haseman-Elston (HE) analysis (LOD score 3.55; P=.00003) and variance-components (VC) analysis (LOD score 2.57; P=.00008). Single-point analyses provided further support for involvement of this locus, with three markers, under the peak of linkage, yielding LOD scores >1.9. The 19q locus was linked to the CELF-R expressive-language score and exceeds the threshold for suggestive linkage under all types of analysis performed-multipoint HE analysis (LOD score 3.55; empirical P=.00004) and VC (LOD score 2.84; empirical P=.00027) and single-point HE analysis (LOD score 2.49) and VC (LOD score 2.22). Furthermore, both the clinical and epidemiological samples showed independent evidence of linkage on both chromosome 16q and chromosome 19q, indicating that these may represent universally important loci in SLI and, thus, general risk factors for language impairment.

Adolescent↗