Genetic Variations in FTSJ1 Influence Cognitive Ability in Young Males in the Chinese Han Population

Human cognitive ability is a trait that is known to be significantly influenced by genetic factors. Previous linkage data provide evidence suggesting that gene FtsJ homolog 1 (Escherichia coli) is associated with mental retardation. The gene may have a relation to individual differences in cognitive ability because it is most critical for brain development. In the present research, three tag single-nucleotide polymorphism (SNPs) (rs2268954, rs2070991, and rs5905692) in FtsJ homolog 1 (E. coli) are selected and genotyped by the PCR-SSCP method. An analysis of variance is performed to determine the relationship between the SNPs and cognitive ability of the Chinese Han population of youth in Qinba mountain. There are significant correlations between the variance in FtsJ homolog 1 (E. coli) and general cognitive ability, verbal comprehension, and preceptual organization. These findings suggest that genetic variations in FtsJ homolog 1 (E. coli) possibly influence human cognitive ability.     

Evidence for Added Value of Baseline Testing in Computer-Based Cognitive Assessment

Context:

Large-scale baseline cognitive assessment for individuals at risk for concussion is a common part of the protocol for concussion-surveillance programs, particularly in sports. Baseline cognitive testing is also being conducted in US military service members before deployment. Recently, the incremental validity of large-scale baseline cognitive assessment has been questioned.

Objective:

To examine the added value of baseline cognitive testing in computer-based neuropsychological assessment by comparing 2 methods of classifying atypical performance in a presumed healthy sample.

Design:

Cross-sectional study.

Setting:

Military base.

Patients or Other Participants:

Military service members who took the Automated Neuropsychological Assessment Matrix (ANAM) before and after deployment (n = 8002).

Main Outcome Measure(s):

Rates of atypical performance in this healthy, active-duty sample were determined first by comparing postdeployment scores with a military normative database and then with each individual''s personal baseline performance using a reliable change index.

Results:

Overall rates of atypical performance were comparable across these 2 methods. However, these methods were highly discordant in terms of which individuals were classified as atypical. When norm-referenced methods were used, 2.6% of individuals classified as normal actually demonstrated declines from baseline. Further, 65.7% of individuals classified as atypical using norm-referenced scores showed no change from baseline (ie, potential false-positive findings).

Conclusions:

Knowing an individual''s baseline performance is important for minimizing potential false-positive errors and reducing the risks and stresses of misdiagnosis.Key Words: Automated Neuropsychological Assessment Metrics, computerized neuropsychological testing, concussions, mild traumatic brain injuries, military athletes

Key Points

• When service members'' predeployment and postdeployment performances on the Automated Neuropsychological Assessment Metrics test were compared using norm-referenced scores and their personal baselines, the absolute rates of atypical performance were similar.
• However, for those individuals whose performance was classified as atypical, a high degree of discordance was noted between the methods. Using norms alone resulted in a high level of false-positive errors.
• Mistakenly classifying an individual as cognitively impaired should be avoided whenever possible because it can lead to overuse of medical resources and undue emotional stress.

Computer-based cognitive testing is fast becoming standard practice in the assessment and management of mild traumatic brain injury (mTBI) in sports and military concussion-management programs. Recommended sport-concussion protocols typically include baseline assessment of cognitive performance for individuals at high risk for concussion, against which postconcussion performance is compared.^1,2 Because of increasing concern for the risk of cognitive injury during military deployment, Congress mandated in 2008 that all US military service members receive computer-based predeployment and postdeployment neuropsychological assessments.³ As with sport-concussion management programs, the purpose of the baseline assessment is to archive the service member''s predeployment neurocognitive performance, so that it can be compared with performance after an injury or other neurologic insult.Such models presume that baseline information is beneficial in determining the presence and severity of cognitive insult after injury by documenting an individual''s level of cognitive functioning before engaging in activities that increase the risk of concussion (eg, sport activity, military deployment). Guskiewicz et al¹ stated that the goal of baseline testing is to provide the most reliable benchmark against which to compare postinjury performance. Without baseline information, clinicians must rely solely on norm-referenced postinjury scores. This practice may increase the risk of false-positive errors in healthy individuals whose premorbid cognitive functioning falls at the lower end of the normal curve. Similarly, this practice may also increase the risk of false-negative errors in injured individuals whose premorbid abilities fall at the higher end of the normal curve, for whom “average” performance relative to norms at a postinjury time point may actually represent a decline.Recently, the empirical validity of concussion-monitoring and management programs for preventing or mitigating risk associated with concussion has been called into question.⁴ Although it is unclear whether these programs mitigate serious risks at the population level, monitoring individuals who have sustained a concussion or other injury is valuable to detect serious cognitive insult, prevent poor outcomes, and optimize return to activity while lowering the risk of future and potentially more damaging injuries. This argument is even more compelling for those individuals who display an atypical recovery course from concussion or other injury and those who have sustained multiple past injuries. In this vein, the utility and added value of large-scale baseline cognitive testing requires demonstration. That is, more information is needed regarding the incremental validity of comparing postinjury cognitive testing with baseline performance over and above the more traditional comparison of postinjury scores with normative values.Although this question is important at both the community and school levels, it becomes even more important in a military context, where population-wide cognitive assessment is standard and false-positive errors have implications for potential overuse of medical and financial resources; in addition, military personnel being screened for possible cognitive impairment may experience undue stress. Thus, we sought to determine the added value of baseline computerized cognitive assessment to decrease potential false-positive errors within a military sample.     

IDS基因高发突变的遗传基础

针对IDS基因具有高发突变和高度遗传异质性的现象,从遗传学角度分析其产生的可能机制,指出:种族、民族的差异,IDS基因结构及其所编码的酶蛋白结构的特殊性,基因所在X染色体的结构的特殊性(含脆性部位)和X染色体的随机失活,突变热点、假基因、隐蔽性拼接位点、indel的存在,以及配子形成过程中复制、修复或交换过程中出现的差错,都可能是导致其高发突变和产生高度遗传异质性的遗传基础.     

IDS基因高发突变的遗传基础

针对IDS基因具有高发突变和高度遗传异质性的现象,从遗传学角度分析其产生的可能机制,指出:种族、民族的差异,IDS基因结构及其所编码的酶蛋白结构的特殊性,基因所在X染色体的结构的特殊性(含脆性部位)和X染色体的随机失活,突变热点、假基因、隐蔽性拼接位点、indel的存在,以及配子形成过程中复制、修复或交换过程中出现的差错,都可能是导致其高发突变和产生高度遗传异质性的遗传基础.     

Predictors of Cognitive Appraisals Following Genetic Testing for BRCA1 and BRCA2 Mutations

The objectives of this study were (1) to describe perceptions of stress and confidence following genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations and (2) to identify predictors of these processes. Participants were 130 high-risk women affected with cancer who received BRCA1/2 test results. Individual difference characteristics and interpersonal factors were measured by self-report before genetic counseling and perceptions of stress and confidence were evaluated by self-report 1 month following disclosure of test results. BRCA1/2 test results had a significant effect only on perceptions of stress (beta = 0.38, p = 0.0001), while trait anxiety had a significant effect on both perceptions of stress (beta = 0.44, p = 0.0001) and confidence (beta = -0.41, p = 0.001). These results suggest that interventions designed to address perceptions of stress related to medical decision-making and familial concerns may need to be targeted to BRCA1/2 mutation carriers and individuals who are highly anxious.     

Assessing Reliability,Heritability and General Cognitive Ability in a Battery of Cognitive Tasks for Laboratory Mice

This report includes the first sibling study of mouse behavior, and presents evidence for a heritable general cognitive ability (g) factor influencing cognitive batteries. Data from a population of male and female outbred mice (n = 84), and a replication study of male sibling pairs (n = 167) are reported. Arenas employed were the T-maze, the Morris water maze, the puzzle box, the Hebb–Williams maze, object exploration, a water plus-maze, and a second food-puzzle arena. The results show a factor structure consistent with the presence of g in mice. Employing one score per arena, this factor accounts for 41% of the variance in the first study (or 36% after sex regression) and 23% in the second, where this factor also showed sibling correlations of 0.17–0.21, which translates into an upper-limit heritability estimate of around 40%. Reliabilities of many tasks are low and consequently set an even lower ceiling for inter-arena or sibling correlations. Nevertheless, the factor structure is seen to remain fairly robust across permutations of the battery composition and the current findings fit well with other recent studies.     

The First Icelandic Family with X-Linked Agammaglobulinemia: Studies of Genetic Markers and Immune Function

This paper describes studies of genetic markers and immune functions in the first Icelandic family identified with X-linked agammaglobulinaemia (X-LA), including three affected brothers. The eldest brother was diagnosed at the age of 9 in 1963. He suffered repeated infections and died at the age of 23. The other two affected brothers, diagnosed at 6 years and 1 year of age, are alive and well on immunoglobulin replacement therapy at the ages of 32 and 24. All were typed for HLA, complement, and various other markers. Pedigree analysis suggests an X-linked segregation of the disease. Their serum IgG is maintained at normal levels on therapy. Several parameters of immune function were studied. The following results were obtained for the X-LA brothers: B cells are absent in their peripheral blood samples. T-cell numbers are normal, but monocytes are increased in numbers and activity. No immunoglobulin production could be elicited in vitro with PWM and no cells containing cytoplasmic Ig were detectable among PWM-stimulated blasts. Nevertheless the proliferative response was particularly vigorous, but the responding cells were shown to be exclusively T cells. No blast transformation could be achieved with EB virus. NK-cell activity was normal/high normal. Other cell-mediated immune functions were normal. In conclusion our data indicate that the differentiation of B cells is blocked in the two surviving X-LA brothers. They have survived for a longer time and in better health than is generally reported. Early diagnosis and adequate replacement treatment with Ig is clearly crucial. Vigorous non-specific immune mechanisms may help to compensate for the defective specific immunity.     

Genetic Evidence of a Functional Monocyte Dichotomy

Human peripheral blood monocytes are found as two distinct populations based upon differential expression of chemokine receptors, adhesion molecules, Fc receptors, and cytokines. cDNA microarray analysis now reveals additional differences between these subsets that suggest dramatically diverse functions. One monocyte subset (CD14++CD16−) appears to be closely paired with neutrophils, and may have as its primary function the removal and recycling of apoptotic neutrophils at sites of inflammation. The other monocyte subset (CD14+CD16+) expresses numerous genes encoding proteins with antimicrobial activity and thus may be more directly involved in peripheral host defense. The production of monocytes capable of efficiently removing dying neutrophils may be necessary to prevent host tissue damage and autoimmune response induction. Therefore, species like humans that produce relatively high levels of circulating neutrophils must also produce relatively high numbers of the recycling monocytes. Conversely, species such as mice and rats that maintain relatively lower levels of circulating neutrophils require fewer recycling monocytes.     

Genetic etiology of nuclear cataract: Evidence for a major gene

Sibling correlations and segregation analysis were used to examine the familial distribution of age-sex-adgusted measures of nuclear sclerosis in 1,247 individuals from 564 sibships in the Beaver Dam Eye Study. There are highly significant sibling correlations for all sibs, and separately for sister-sister, sister-brother, and brother-brother pairs. Two transformed normal distributions give the best fit to the data. The hypothesis of mendelian transmission of a major effect cannot be rejected, but the hypothesis of a random environmental major effrect is rejectd. The parameters of the τAB free model showed close similarity to the values expected under a mendelian hypothesis. Our results suggest that a single major gene can account for 35% of the total variability of age-sex-adjusted measures of nuclear sclerosis. © 1993 Wiley-Liss, Inc.     

Use of Genetic Testing for Primary Immunodeficiency Patients

Genetic testing plays a critical role in diagnosis for many primary immunodeficiency diseases. The goals of this report are to outline some of the challenges that clinical immunologists face routinely in the use of genetic testing for patient care. In addition, we provide a review of the types of genetic testing used in the diagnosis of PID, including their strengths and limitations. We describe the strengths and limitations of different genetic testing approaches for specific clinical contexts that raise concern for specific PID disorders in light of the challenges reported by the clinical immunologist members of the CIS in a recent membership survey. Finally, we delineate the CIS’s recommendations for the use of genetic testing in light of these issues.     

Knowledge About Genetic Risk for Breast Cancer and Perceptions of Genetic Testing in a Sociodemographically Diverse Sample

Informed consent for genetic testing for breast–ovarian cancer susceptibility requires that women understand basic concepts about the inheritance of cancer susceptibility and the benefits and risks associated with genetic testing. Women awaiting routine medical services (N = 220) were surveyed about their knowledge of breast cancer and cancer genetics and their perceptions of genetic testing and personal risk. There were no racial differences in median income or mean level of education. Compared to Caucasian women, African American women knew significantly less about breast cancer and about genetic risk for breast cancer. African American women had different psychological, social, and economic concerns as evidenced by how they weighted the benefits and risks of genetic testing. This study is the first to assess several dimensions of informed consent for genetic testing among a sociodemographically diverse group. The findings should enable health professionals to target the African American and lower-income populations with the appropriate education and counseling.     

Comorbidity of Mathematics and Reading Deficits: Evidence for a Genetic Etiology

In order to assess the genetic etiology of the comorbidity of reading and mathematics difficulties, data were ascertained from two samples: (1) 102 identical and 77 same-sex fraternal twin pairs in which at least one member of each pair is reading disabled and (2) 42 identical and 23 same-sex fraternal twin pairs in which at least one member is math disabled. Composite reading and mathematics performance data from each sample were fitted to the basic multiple regression model for the analysis of selected twin data and its bivariate extension. Resulting estimates of bivariate heritability and the genetic correlation between the reading and the mathematics performance measures suggest that the comorbidity between mathematics and reading difficulties is due in part to genetic influences.     

Hereditary Lewy-Body Parkinsonism and Evidence for a Genetic Etiology of Parkinson''s Disease

The first systematic genetic study of Parkinson's disease (PD) was carried out by Mjönes in 1949. His results indicated autosomal dominant transmission with 60% penetrance. These conclusions, however, were long discounted because oligosymptomatic and atypical relatives were counted as secondary cases without clear justification. Subsequent surveys of patient and twin studies failed to confirm evidence of familial concentration and the hypothesis of a genetic etiology was over-shadowed by interest in possible environmental neurotoxins. A growing accumulation of pedigrees of histologically confirmed Lewy-body PD over the past several years has refocused attention on genetic factors. Fluorodopa positron emission tomagraphy (PET) studies in oligosymptomatic co-twins of probands and recent clinicopathologic studies of atypical cases have provided retrospective support for Mjönes' methodology. A survey of a personal series of PD patients showed that the majority of those for whom pedigree information was available were familial. This along with another recently reported series confirm Mjönes' data showing similar segregation ratios for siblings and parents, a low ratio of maternal: paternal transmission and a marked asymmetry in the distribution of ancestral secondary cases. These findings favor monogenic autosomal dominant inheritance and show reason to argue against a multifactorial etiology or heteroplasmy. The clinical evidence justifies searching for gene loci linked to PD. Available methods are briefly outlined. Preliminary investigations have examined possible allelic associations, e.g., with alleles of MAO-A and debrisoquine hydroxylase and linkage to the tyrosine hydroxylase gene on chromosome 11p15.5 has been excluded in one study of juvenile familial parkinsonism. Linkage mapping studies are presently underway.     

Predictive Genetic Testing: High Risk Expectations in the Face of Low Risk Information

The aims of this cross-sectional, questionnaire study were (1) to estimate the proportion of those receiving negative (low risk) results following predictive genetic testing who expect to undergo clinically unnecessary future screening and (2) to examine the factors associated with this expectation. Of 127 adults receiving negative results following predictive genetic testing for familial adenomatous polyposis (FAP), 54 people (42%) were expected to attend for future bowel screening. The main predictor was doubt about the accuracy of genetic test results. Expecting to attend was also associated univariately with perceiving the chance of developing FAP as higher, being more worried about this, perceiving the test result to be more uncertain and threatening, and holding a behavioral model of the cause of FAP. Attendance for health screening may be influenced by people's perception of the accuracy of genetic tests that they have undergone. Future research should investigate test presentation and influences on test perception.     

Variation in Attraction to Host Plant Odors in an Invasive Moth Has a Genetic Basis and is Genetically Negatively Correlated with Fecundity

Lepidopteran insects are major pests of agricultural crops, and mated female moths exploit plant volatiles to locate suitable hosts for oviposition. We investigated the heritability of odor-guided host location behavior and fecundity in the cosmopolitan oriental fruit moth Grapholita (Cydia) molesta, an oligophagous herbivore that attacks fruit trees. We used a full-sib/half-sib approach to estimate the heritability and the genetic correlation between these two traits. Results document a considerable genetic basis for olfactory attraction of females (h ²  = 0.37 ± 0.17) and their fecundity (h ²  = 0.32 ± 0.13), as well as a genetic trade-off between female attraction and fecundity (r _g  = −0.85 ± 0.21). These estimations were empirically corroborated by comparing two strains maintained in the laboratory for different numbers of generations. The long-term reared strain lost its olfactory discrimination ability but achieved significantly higher fecundity compared with the short-term reared strain. Our results highlight that genetic studies are relevant for understanding the evolution of odor-guided behavior in herbivore insects and for judging the promise of pest management strategies involving behavioral manipulation with plant volatiles.     

Methodological Guidelines for Genetic Safety Testing of Cell Transplants

A combination of karyotyping and aneuploidy analysis by interphase fluorescent in situ hybridization is a sensitive method for evaluation of genetic stability of stem cell cultures. The methodology and specific features of preparing and analyzing the cytogenetic preparations are described as exemplified by human multipotent mesenchymal stromal cells.