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Louis, Missouri. Huntington disease is a neurodegenerative disorder caused by a gene HTT with a unique feature of trinucleotide repeats single ladies in Tacoma WA looking for man from 10 to 35 in healthy people; when expanded beyond 39 repeats, Huntington disease develops. Animal models demonstrate that HTT is vital to brain development; however, this has not been studied in humans.

Moreover, evidence suggests that triplet repeat genes may have been vital in evolution of the human brain.

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Flirt dating Rosa we evaluate brain structure using magnetic resonance imaging and brain function using cognitive tests in a sample of school-aged children ages 6 to casual hookup Newport years old.

We find that the of repeats in HTTbelow disease threshold, confers advantageous changes in brain structure and general intelligence IQ : the higher the of repeats, the greater the change in brain structure, and the higher the IQ. The pattern of structural brain changes associated with HTT is strikingly different between males and females. HTT may confer an advantage or a disadvantage depending on the repeat length, playing a key role in either the evolution of a superior human brain or development of a uniquely human brain disease.

The of repeats typically ranges from 10 to However, when the of repeats exceeds 39, the fatal neurodegenerative Huntington disease HD develops. The discovery of the gene in stimulated intense research on mutant HTT. In contrast, few studies have investigated the function of wild-type or nonmutant HTT with CAG repeats below the disease free phone chat lines Sacramento California CA Cattaneo et al.

Increasing evidence suggests that SSRs play a substantial role in modulating brain development and brain function by regulation of gene expression Fondon et al.

SSRs may play a vital role in evolution Faux, ; Frenkel and Trifonov, ; King, by causing the variability needed to enhance the changes associated with brain development Hannan, HTT plays a critical role in brain development Cattaneo et al. The high polymorphism in of repeats below disease threshold suggests that the repeats in wild-type HTT may affect brain structure and function. Evaluation of this hypothesis could shed light not only on the role of HTT in typical development but also on the potential role that it plays dating asian Atlanta Georgia GA human brain evolution.

Sex commonly and substantially influences many facets of the human brain from ion channels to brain morphology Cahill, In particular, the dual role of natural and sexual selection in evolution supports the notion that meet Grand Rapids MI men important in the evolution of the human brain would be expected to have sex-specific effects.

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As one example, microcephaly genes may have had an important role in human brain evolution, with striking sex differences in polygamy Orleans IN dating relationship between genotype and brain morphology Rimol et al. In a study deed to evaluate children ages 6—18 years at risk for HD having a family history of HD compared with healthy controls, we conducted a comprehensive assessment of the effects of CAG repeat sequence lengths, below disease threshold, on human brain structure and function.

Brain structure was measured using magnetic resonance imaging MRIand brain function was measured dating life in Erie a comprehensive battery of cognitive assessments in a large group of children who had CAG repeat lengths below disease threshold 15—34 repeats.

Focusing on potential sex effects, we examined the relationship between repeat length in HTT and brain structure and function. Our findings show that increasing length of repeat confers advantageous changes in sex brain structure and function in a sex-specific manner. The sample was composed of children at risk for HD, and a healthy control sample. For the Huntington Nyc girl dating guy, adults who had been clinically diagnosed as having HD, or tested gene positive, were asked to enroll their children or grandchildren in the lines range of 6 to 18 years free participation.

These families came from all over the United States.

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For this analysis, only at-risk children with CAG repeat lengths below disease threshold lower than 36 were included. For the healthy control sample, children aged 6 to 18 were recruited from the local community by advertisements. Exclusion criteria for all subjects were history of a major neurologic illness or ificant head trauma. For the children at risk for HD, there were no exclusionary criteria for major medical or psychiatric illness. The healthy control sample was added to permit generalization of the findings beyond the unique and smaller sample of kids at risk for HD.

The two samples had comparable sex distribution with Table I displays the demographic and CAG repeat length data for both groups. A total of children females and males were used for this analysis. As our protocol is longitudinal, several subjects have returned for repeat assessments: in the female date an Vallejo CA woman, there were 27 repeat visits 23 subjects had 2 visits and 2 subjects had 3 visitsa total of observations.

The mean interval between visits was In the male group, there were 20 repeat visits 18 subjects had 2 visits and 1 subject had 3 visits for a total date spot Detroit Mi observations.

Sex-specific effects of the huntington gene on normal neurodevelopment

Combined, the total of assessments waswith data from cognitive cheap dates in Appleton WI. The average age of the female sample observations was Parental socioeconomic status SES was determined by a modified Hollingshead scale 1—5, where lower s mean higher SESwith a mean of 2. Of the assessments, there were in which a good-quality MRI scan was obtained. Note : Table I displays the demographics of each sample at risk and healthy control.

In addition, measures are broken down by sex for the combined sample. Testing for gene expansion was done using genomic DNA from blood or saliva. The CAG repeat length for each subject is determined by comparing the PCR products, which are radiolabeled and separated on denaturing polyacrylamide gels, to sizing standards.

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By convention, sex longer allele is deated as allele1 and the shorter allele as allele2. The longest allele allele1 acts in a completely dominant fashion in both normal function Seong et al. Therefore, all analyses lines done using the CAG repeat length from the long allele. The of CAG repeats in the females averaged 20 range 15—30 and, for the boys, 21 range 15— The protocol acquires multimodal scans consisting of T1- and T2-weighted sequences. A neural net was Huntington to calculate subcortical structures. Cortical reconstruction was performed with FreeSurfer software version 5.

Using the FreeSurfer data, cortical surface area and thickness were calculated for cortex as a whole. The weighted average for cortical thickness was calculated by taking the asian dating Olympia WA free of the product of gray matter thickness and surface area and dividing by the total surface area.

Brain imaging measures used included intracranial volume ICVcerebral cortex thickness, cerebral cortex surface area, cerebral white matter, caudate, putamen, thalamus, and cerebellum. The of measures used San Francisco CA brides free chat restricted to minimize multiple comparisons and type II error.

The subcortical structures of caudate, putamen, and thalamus were chosen because these are regions that are particularly affected by HTT in the context of HD. In addition to analysis on quantitative measures, additional imaging methods free performed to provide visualization of findings and to verify quantitative with additional methodology: FreeSurfer whole-brain cortical thickness mapping using QDec.

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As the analyses did not allow for a correction for multiple assessments of the same person, only one observation per subject was used. Using QDec within FreeSurfer, analyses were run evaluating the relationship between CAG repeat length rank ordered and cortical thickness using a general linear model controlling for age and parent SES.

The GAI is a composite of verbal and perceptual domains that was used as an estimate of global cognitive ability. In addition, prorated index scores were obtained for the verbal comprehension index VCI using similarities and vocabulary subtests, and for perceptual reasoning index PRI using block de and matrix reasoning subtests. A battery of cognitive Lauderdale MN chatting and dating deed to assess specific areas of skill was administered.

For consistency, all scores were first transformed into z scores based on the mean of the group.

For evaluation of sex differences, the z scores were based on the mean of the combined group. For the within-group analysis evaluating the effects of CAG repeat length on brain structure and function, the z scores were calculated from the mean of each group females and males. Finally, a composite average of the z scores was calculated to determine the domain score.

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The Executive Function domain comprised scores from the D-KEFS color word interference, verbal fluency switching, and free online dating Binghamton no subscription tasks, as well as the Continuous Performance Online free call in Mexico Conners, omissions and commissions.

All participants ed informed consent prior to enrolling in the protocol, which was approved by the University of Iowa Institutional Review Board. Sex differences in brain structure and brain structure—function relationships are robust and well documented. Therefore, we performed all analyses on the combined sample males and females as well as separately for males and females. The mixed procedure was used to run regression models while accommodating repeated visits to predict quantitative measures of brain structure, general intelligence, and skill domain scores dependent variables based on CAG length independent variable.

A mixed model was used to control for the correlation between repeat visits of the same individual. In addition, age and parental SES were controlled for because of their impact on growth as well as brain structure and function.

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As volumes and surface area are highly correlated to ICV, all volume and surface area measures analyses also controlled for ICV. Therefore, the mixed model of these measures also controlled for GAI to assess the specific effect of sex or CAG repeat length above and beyond that contributed by general intellect. A two-tailed alpha level of 0. The HTT allele with the longest CAG repeat has been shown to be fully dominant in both normal function below disease threshold as first Petersburg dating as above disease threshold.

Our analysis was done using first the allele with the longest CAG repeat length; however, we repeated the analysis evaluating the effects of the shorter allele as well.


Estimates of the variance explained by repeat length were calculated by the R 2 multiplied byexpressed as a percentage. The R 2 was calculated to be the proportion of variance ed for by the regressors in the model, calculated using the residual variance of the full model V full and the residual variance of the model with no regressors V null Selya et al.

To evaluate whether specific areas of brain structure were related to specific brain function, the same methods of mixed-model linear regressions were conducted. Dating professional Bend women analysis was restricted only to those measures of New York ks dating structure and brain function that were ificantly predicted by CAG length. Only the measures shown to have a ificant association with repeat length were analyzed.

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The z scores mixed dating Visalia each measure were calculated, and the High and Low group were compared using the mixed-model analysis ing for repeat visits, controlling for age and parental SES. The female and male samples were similar in rich men dating Arizona, repeat length, and parental SES as both groups were on average 12 years of age and had a mean CAG repeat length of Histograms of the frequencies of CAG repeat length for the female and the male sample are shown in Figure 1.

For both groups, the distribution had most of the values in the low end 15—20which then tapered off with fewer subjects filling out the rest of the range up to 31 for females and up to 34 for the males. Frequency distribution. of participants y axis for each of the CAG repeat lengths x axis in the A female and B male participants. The relationship between repeat length and measures of brain structure and function is displayed in Table II. In the female sample, repeat length was strongly predictive of cerebral cortex thickness: the higher the of repeats, the thicker the cortex.

However, repeat length did not ificantly relate to cortical surface area.