The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size.

Prior studies describing the relationship between CAG size and the age at onset of Huntington disease (HD) have focused on affected persons. To further define the relationship between CAG repeat size and age at onset of HD, we now have analyzed a large cohort of affected and asymptomatic at-risk persons with CAG expansion. This cohort numbered 1,049 persons, including 321 at-risk and 728 affected individuals with a CAG size of 29-121 repeats. Kaplan-Meier analysis has provided curves for determining the likelihood of onset at a given age, for each CAG repeat length in the 39-50 range. The curves were significantly different (P < .0005), with relatively narrow 95% confidence intervals (95% CI) (+/-10%). Penetrance of the mutation for HD also was examined. Although complete penetrance of HD was observed for CAG sizes of > or = 42, only a proportion of those with a CAG repeat length of 36-41 showed signs or symptoms of HD within a normal life span. These data provide information concerning the likelihood of being affected, by a specific age, with a particular CAG size, and they may be useful in predictive-testing programs and for the design of clinical trials for persons at increased risk for HD.     

Craniofacial variation and growth in the Prader-Labhart-Willi syndrome

A study of anthropometric variation and craniofacial growth in individuals with the Prader-Labhart-Willi syndrome (PLWS) illustrates the utility of anthropometry in clinical evaluation and research. Anthropometric measurements, including head length and breadth, minimum frontal diameter, and head circumference, were obtained on 38 PLWS individuals (21 with chromosome 15 deletions) with an age range from 2 weeks to 39 years. No anthropometric differences were found between the two chromosome subgroups. A relative deceleration in the growth of certain craniofacial dimensions (head circumference and length) is suggested by the negative correlations between age and Z-scores for the measurements. Raw values for minimum frontal diameter and head breadth were near or below the 5th percentile curve, while almost all values for head length and circumference fell within normal limits. The data support suggestions that dolichocephaly be considered an early diagnostic feature of PLWS. Furthermore, the status of narrow bifrontal diameter as a major feature of PLWS is confirmed.     

Heritability of anthropometric phenotypes in caste populations of Visakhapatnam,India

In this study, we used anthropometric data from six Andhra caste populations to examine heritability patterns of 23 anthropometric phenotypes (linear, craniofacial, and soft tissue measures) with special reference to caste differences. We obtained anthropometric data from 342 nuclear families from Brahmin, Reddy, Telaga, Nagara, Ag. Kshatriya, and Mala castes of Visakhapatnam, India. These caste groups represent the existing hierarchical stratification of Indian populations. We used a variance components approach to determine the heritability (h2) of these 23 anthropometric phenotypes (height, weight, BMI, etc.). The sample consisted of 1918 individuals ranging in age from 6 to 72 years (mean = 21.5, S.D. = 13.8). The heritabilities (h2 +/- S.E.) for all anthropometric traits for the entire sample were significant (p < 0.0001) and varied from 0.25 +/- 0.05 (BMI) to 0.61 +/- 0.05 (bizygomatic breadth) after accounting for sex, age, and caste effects. Since data on socioeconomic and nutritional covariates were available for a subset of families, we repeated the genetic analyses using this subset, which has yielded higher heritabilities ranging from 0.21 +/- 0.16 (head breadth) to 0.72 +/- 0.18 (nasal breadth). In general, craniofacial measurements exhibited higher h2 compared to linear measures. Breadth measurements and circumferences yielded more or less similar heritabilities. Age and sex effects were significant (p < 0.0001 ) for most of the traits, while the effects of caste, socioeconomic status, and nutritional status were inconsistent across the traits. In conclusion, anthropometric phenotypes examined in this study are under appreciable additive genetic influences.     

亨廷顿病的基因诊断

为了简单高效检测HD基因开放阅读框5’端(CAG)ｎ三核苷酸重复序列,建立快速准确的亨廷顿病(Huntington disease, HD)基因诊断方法,应用TaKaRa LA Taq DNA聚合酶配合GC buffer扩增HD基因包含(CAG)ｎ重复序列的目的片段,非变性聚丙烯酰胺凝胶电泳检测后回收(CAG)ｎ拷贝数异常增多的目的片段,再次PCR扩增后将产物连接至T载体,进行DNA测序确定CAG的拷贝数。应用该方法对一个HD家系的3名成员以及20名正常人进行基因诊断,结果显示该HD家系3名成员的一条染色体上的(CAG)ｎ拷贝数在正常范围内,而另一条染色体上的(CAG)ｎ拷贝数异常增多,分别为39、40、41,而20例正常人(CAG)ｎ拷贝数均在正常范围内,正常和HD等位基因之间的(CAG)ｎ拷贝数不相重叠。因此,应用该方法可以对HD进行准确的基因诊断,结果同时也证明HD基因的动态突变是导致中国人亨廷顿病的遗传基础。     

Comparative study of normal, Crouzon, and Apert craniofacial morphology using finite element scaling analysis

Finite element scaling analysis is used to study differences in morphology between the craniofacial complex of normal individuals and those affected with the syndromes of Apert and Crouzon. Finite element scaling quantifies the differences in shape and size between forms without reference to any fixed, arbitrary registration point or orientation line and measures the amount of form change required to deform one object into another. Two-dimensional coordinates of landmarks digitized from annual sets of cephalometric radiographs were used in the analysis. A simple tabulation shows no difference in variances between the normal and pathological samples. A test of mean differences depicts the Apert and Crouzon morphologies as significantly different from normal. The Apert palate differs from normal in shape in the older age groups analyzed, and palatal size differences are most common at the posterior nasal spine. The Apert pituitary fossa and basi-occiput are significantly larger than normal. The Crouzon pituitary fossa is also larger than normal, but the difference is not always significant. The typical morphology of the Crouzon nose is due more to differences in shape than size. The Crouzon basi-occiput is significantly smaller than normal. An age association of the differences between the normal and pathological craniofacies was found in Apert syndrome but not in Crouzon syndrome. Apert syndrome is characterized by a more homogeneous pattern of craniofacial dysmorphology from 6 months to 18 years of age than Crouzon syndrome.     

Craniofacial anthropometric analysis in Down's syndrome patients

Past investigations of Down's syndrome (DS) have indicated that there are marked abnormalities in the craniofacial morphology. The aim of this study was to establish the craniofacial anthropometric variables which discriminate DS group from healthy population and also to observe the changes occurring with growth. Using noninvasive method of craniofacial anthropometry, craniofacial pattern profile (CFPP) analysis (from twenty-five anthropometric measurements per person) was performed in 104 DS individuals and 365 healthy controls, aged seven to fifty-seven and divided into four age ranges. Z-scores were calculated for each variable and the variations in the craniofacial region have been identified by multivariate discriminative analysis. The results showed that three variables (head length (g-op), head circumference (OFC) and outer canthal distance (ex-ex) were responsible for 85.68% variability (p < 0.001). The analysis of z-scores showed that the majority of variables were in subnormal (under -2 SD) and normal range (from -2SD to +2SD), but none of them was in the supernormal range (over the +2SD). Some craniofacial characteristics are age-related. On the basis of craniofacial anthropometric traits it was possible to separate even 91.35% of DS patients from the healthy population. It could be concluded that these findings demonstrate the usefulness of application of CFPP in defining abnormal craniofacial dimensions in DS individuals.     

Creatinine versus specific gravity-adjusted urinary cadmium concentrations

The aim was to assess how urinary creatinine is affected by age, gender, body size and meat intake, and to determine to what extent such factors might affect the creatinine adjustment of urinary cadmium. The study was based on three Swedish studies: (1) 67 non-smoking women aged 20–50 years (24-h urine samples); (2) 289 men and 434 women aged 16–81 years (spot urine samples); and (3) 98 men and 105 women aged 19–72 years (spot urine samples). The effects of age, body surface area (as an indicator of muscle mass), and meat intake on urinary creatinine and cadmium were analysed using multiple regression analyses. Gender- and age-related variations in urinary creatinine and cadmium adjusted for creatinine or specific gravity were compared by ANOVA or ANCOVA. In the multiple regression analyses, body surface area, gender, age and meat intake were the major determinants of urinary creatinine. Urinary cadmium adjusted for creatinine and specific gravity were also dependent on body size, gender and age. Urinary cadmium adjusted for creatinine was 15–92% higher in women or older individuals than in men or younger individuals. Women or older individuals had –3 to 79% higher urinary cadmium adjusted for specific gravity than men or younger individuals had, and such a difference between gender or age group was less obvious in specific gravity adjustment than in creatinine adjustment. Thus, urinary cadmium adjusted for creatinine is more affected by age, gender, body size and meat intake than is specific gravity adjustment. When comparing individuals or populations with large differences in muscle mass or meat intake, such effects can be especially important. In such studies, specific gravity adjustment seems to be more appropriate.     

Creatinine versus specific gravity-adjusted urinary cadmium concentrations

The aim was to assess how urinary creatinine is affected by age, gender, body size and meat intake, and to determine to what extent such factors might affect the creatinine adjustment of urinary cadmium. The study was based on three Swedish studies: (1) 67 non-smoking women aged 20-50 years (24-h urine samples); (2) 289 men and 434 women aged 16-81 years (spot urine samples); and (3) 98 men and 105 women aged 19-72 years (spot urine samples). The effects of age, body surface area (as an indicator of muscle mass), and meat intake on urinary creatinine and cadmium were analysed using multiple regression analyses. Gender- and age-related variations in urinary creatinine and cadmium adjusted for creatinine or specific gravity were compared by ANOVA or ANCOVA. In the multiple regression analyses, body surface area, gender, age and meat intake were the major determinants of urinary creatinine. Urinary cadmium adjusted for creatinine and specific gravity were also dependent on body size, gender and age. Urinary cadmium adjusted for creatinine was 15-92% higher in women or older individuals than in men or younger individuals. Women or older individuals had -3 to 79% higher urinary cadmium adjusted for specific gravity than men or younger individuals had, and such a difference between gender or age group was less obvious in specific gravity adjustment than in creatinine adjustment. Thus, urinary cadmium adjusted for creatinine is more affected by age, gender, body size and meat intake than is specific gravity adjustment. When comparing individuals or populations with large differences in muscle mass or meat intake, such effects can be especially important. In such studies, specific gravity adjustment seems to be more appropriate.     

Dynamic membrane studies in individuals at risk for Huntington's disease

Lymphocyte plasma membrane dynamics were studied by energy-transfer polarization in twenty-three neurologically normal individuals at-risk for Huntington's disease (HD). The results were compared to 10 normal controls and 10 known HD patients. The normal and HD subjects segregated into two distinct groups. The at-risk group had findings distributed along a continuum with values similar to known HD patients or to normal controls. These findings suggest that further studies of membrane dynamics will contribute to understanding the molecular defect in HD and to the development of a potential molecular marker.     

Creatinine versus specific gravity-adjusted urinary cadmium concentrations.

The aim was to assess how urinary creatinine is affected by age, gender, body size and meat intake, and to determine to what extent such factors might affect the creatinine adjustment of urinary cadmium. The study was based on three Swedish studies: (1) 67 non-smoking women aged 20-50 years (24-h urine samples); (2) 289 men and 434 women aged 16-81 years (spot urine samples); and (3) 98 men and 105 women aged 19-72 years (spot urine samples). The effects of age, body surface area (as an indicator of muscle mass), and meat intake on urinary creatinine and cadmium were analysed using multiple regression analyses. Gender- and age-related variations in urinary creatinine and cadmium adjusted for creatinine or specific gravity were compared by ANOVA or ANCOVA. In the multiple regression analyses, body surface area, gender, age and meat intake were the major determinants of urinary creatinine. Urinary cadmium adjusted for creatinine and specific gravity were also dependent on body size, gender and age. Urinary cadmium adjusted for creatinine was 15-92% higher in women or older individuals than in men or younger individuals. Women or older individuals had -3 to 79% higher urinary cadmium adjusted for specific gravity than men or younger individuals had, and such a difference between gender or age group was less obvious in specific gravity adjustment than in creatinine adjustment. Thus, urinary cadmium adjusted for creatinine is more affected by age, gender, body size and meat intake than is specific gravity adjustment. When comparing individuals or populations with large differences in muscle mass or meat intake, such effects can be especially important. In such studies, specific gravity adjustment seems to be more appropriate.     

Inverse relationship between age at onset of Huntington disease and paternal age suggests involvement of genetic imprinting.

It is well recognized that age at onset of Huntington disease (HD) is strongly influenced by the sex of the affected parent, and this has lead to suggestions that genetic imprinting or maternal specific factors may play a role in the expression of the disease. This study evaluated maternal and paternal ages, birth order, parental age at onset, and sex of the affected parent and grandparent in 1,764 patients in the National HD Roster by using linear-regression techniques which incorporated a weighted least-squares approach to accommodate the correlation among siblings. It was found that paternal age is negatively associated with age at onset of HD, particularly among subjects who inherit the mutant gene from grandfathers. Apparent associations between age at onset and birth order and between age at onset and maternal age were not significant after adjustment for paternal age. The paternal age effect is strongest among juvenile-onset cases and individuals with anticipation of greater than or equal to 10 years, although it is detectable across the entire age-at-onset distribution. The tendency for older fathers, including those not transmitting the HD gene, to have affected offspring with early-onset disease may be consistent with a gene imprinting mechanism involving DNA methylation. Because paternal age in unaffected fathers is also a significant determinant of age at onset, methylation in this context might involve HD modifier genes or the normal HD allele.     

A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS study

Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h²=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21–23 (LOD=2.29), and 6q24–26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.     

Genetic drift and anthropometric variation in Ireland

The effect of genetic drift on the genetic structure of seven Irish populations was investigated using anthropometric data collected during the 1890s on 259 adult males. These populations ranged in size from 769 to 3757, were relatively stable over time, and were located within 119 km of one another. Two populations are known to have experienced considerable English admixture. Data on ten anthropometric variables (three body measures and seven craniofacial measures) were adjusted for age and used to compute a relationship (R) matrix. The R matrix was converted into a distance measure and compared with a potential genetic drift distance measure, defined as (1/Ni + 1/Nj), where Ni and Nj are the effective population sizes of groups i and j (derivation of this formula is presented). Distances were rank-transformed, and the correlation between their pairwise elements was computed using matrix permutation methods to assess significance. Under the hypothesis that drift affects anthropometric variation, these correlations are expected to be positive. The correlation between anthropometric distance and potential genetic drift distance is 0.123, which is not significantly different from 0 (P = 0.368). When a multiple regression model is used to adjust for geographic distance and English admixture, the partial correlation (0.369) is significant (p = 0.021). As part of further analysis of the genetic structure of these populations, the same analyses were repeated using a distance matrix derived from surname frequencies. The correlation of surname distance and potential genetic drift distance is 0.164, which is not significant (p = 0.264). When the multiple regression model is applied, the correlation is 0.401, which is borderline significant (p = 0.055). These results show the influence of genetic drift, local migration, and admixture on Irish population structure.     

Age variations in anthropometric and body composition characteristics and underweight among male Bathudis--a tribal population of Keonjhar District, Orissa, India

A cross-sectional study of 226 male Bathudis, a tribal population of Keonjhar District, Orissa, India, was undertaken to investigate age variations in anthropometric and body composition characteristics and the frequency of underweight. The subjects were categorized into three age groups: Group I: < 30 years, Group 11: 30-49 years, Group III: 2 50 years. Height, weight, circumferences and skinfolds data were collected. Body mass index (BMI) and several body composition variables and indices were derived using standard equations. Results revealed that there existed significant negative age variations for most of the anthropometric and body composition variables and indices. Correlation studies of age with these variables and indices revealed significant negative correlations. Linear regression analyses revealed that for all these variables, age had a significant negative impact. It was also observed that with increasing age, there was an increase in the frequency of underweight individuals. In conclusion, this study showed that among Bathudi men, age was significantly negatively related with anthropometric and body composition variables and indices. Furthermore, with increasing age, the frequency of underweight individuals increased.     

Identification of Hemoglobin Levels Based on Anthropometric Indices in Elderly Koreans

ObjectivesAnemia is independently and strongly associated with an increased risk of mortality in older people and is also strongly associated with obesity. The objectives of the present study were to examine the associations between the hemoglobin level and various anthropometric indices, to predict low and normal hemoglobin levels using combined anthropometric indices, and to assess differences in the hemoglobin level and anthropometric indices between Korean men and women.MethodsA total of 7,156 individuals ranging in age from 53–90 years participated in this retrospective cross-sectional study. Binary logistic regression (LR) and naïve Bayes (NB) models were used to identify significant differences in the anthropometric indices between subjects with low and normal hemoglobin levels and to assess the predictive power of these indices for the hemoglobin level.ResultsAmong all of the variables, age displayed the strongest association with the hemoglobin level in both men (p < 0.0001, odds ratio [OR] = 0.487, area under the receiver operating characteristic curve based on the LR [LR-AUC] = 0.702, NB-AUC = 0.701) and women (p < 0.0001, OR = 0.636, LR-AUC = 0.625, NB-AUC = 0.624). Among the anthropometric indices, weight and body mass index (BMI) were the best predictors of the hemoglobin level. The predictive powers of all of the variables were higher in men than in women. The AUC values for the NB-Wrapper and LR-Wrapper predictive models generated using combined anthropometric indices were 0.734 and 0.723, respectively, for men and 0.649 and 0.652, respectively, for women. The use of combined anthropometric indices may improve the predictive power for the hemoglobin level.DiscussionAmong the various anthropometric indices, with the exception of age, we did not identify any indices that were better predictors than weight and BMI for low and normal hemoglobin levels. In addition, none of the ratios between pairs of indices were good indicators of the hemoglobin level. Finally, the Korean men tended to have higher associations between the anthropometric indices and anemia than the women.     

鲫耳石重量与年龄的关系及其在年龄鉴定中的作用

耳石重量在年龄组间重叠较少,大小相近的个体,年龄大的,即生长慢的耳石重量比年龄小的,即生长快的大,不同龄组之间耳石重量有显著差异（P＜0．05）,按年龄组在耳石重量与相应的体长作图,可初步判断观测年龄的可靠性,分析耳石重量频率分布能分离出体长相近,年龄不同的个体,其结构与耳石年轮观测的基本一致,耳石重量与年龄呈显著线性正相关（P＜0．05）,用耳石重量与年龄关系估算的年龄从耳石上直接读取的年龄无显著差异（P＞0．05）,文中对耳石重量直接用于确定鱼类年龄的可能性作了分析和探讨。     

Obesity and Blood Pressure in children

Estimates of relationships between blood pressures and anthropometric structure or body composition were made on a total sample of 414 children, taking age and sex into account. A subsample of 250 children was formed from obese (or slightly obese) subjects. A different pattern in anthropometric structure and body composition resulted in relation to a different degree of obesity. A canonical correlation analysis was carried out for each sex, in which a multivariate measure of the linear association between heart-circulatory functionality parameters, on the one hand, and all the anthropometric traits and body composition parameters, on the other, was computed. This association resulted statistically significant in both sexes, also if a difference was observed as concerns the traits that most heavily contributed to the relation-ships between sets of variables, with an evident sexual dimorphism also in infancy. The necessity of preventive measures and sanitary screening also during infancy was pointed out.     

Cross-sectional changes in anthropometric variables among Wapishana and Patamona Amerindian adults

Although anthropometric information on South American Indian populations has been collected for many years, remarkably little is known about age-related changes in their body size in adulthood. The lack of baseline information on the normal pattern of aging among Amerindian adults hinders investigations into the health consequences of the many economic, environmental and demographic changes that are currently occurring among South American Indian populations. This study presents data on the body size and shape of a convenience sample of 345 Patamona and 186 Wapishana Amerindian adults over 20 years of age living in the remote interior of Guyana. Analysis of the cross-sectional data demonstrated significant declines in stature, sitting height, and biacromial width with age, while there were no changes in subischial leg length or arm length across the age range of the study populations. In contrast, body weight and body mass index (BMI--a measure of body fatness) only declined in those over 50 years of age, after a period of increase. Significant differences in adult linear body dimensions were found between the two Amerindian populations that were proposed to be the result of known differences in childhood growth performance. However, the greater BMI of the Wapishana was shown to be associated with their significantly greater current wealth, thereby highlighting the presence of biological consequences of wealth inequalities even within these subsistence farming populations.     

A cephalometric study in Rubinstein-Taybi syndrome

A roentgencephalometric study to compare the facial morphology of 18 individuals affected with Rubinstein-Taybi syndrome and 25 of their parents was performed. The main findings in the affected individuals were shortening of facial height and depth, cranial base length, a marked decrease in size of the mandible, and a steep cranial base. A change with age was found for some dimensions. The pattern variability indices were high, indicating an abnormal craniofacial profile. The correlations between most patients were high, although this was less expressed for the younger patients. The parents had a normal pattern profile and pattern profile variability indices. The correlation between parents and their affected children was low. This study suggests that pattern profile analysis of cephalometric measurements may be a useful diagnostic tool in Rubinstein-Taybi syndrome. However, comparable studies of large groups of patients, especially of a younger age, are needed for further ascertainment of normal values in individuals with Rubinstein-Taybi syndrome at different stages of facial development.     

Copper distribution in the normal human brain

Copper concentration was determined in samples from 38 areas of 7 normal human brains. The grey matter contained higher concentrations of copper than the white matter. Identical areas of the grey and white matter of the cerebral cortex showed significant differences between individuals. In the caudate nucleus the highest concentrations of copper were found in the tail followed by the body and the head, respectively. A negative linear regression between age and brain copper levels was demonstrated.