Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections

Chromosomal deletions or reciprocal duplications of the 16p13.1 region have been implicated in a variety of neuropsychiatric disorders such as autism, schizophrenia, epilepsies, and attention-deficit hyperactivity disorder (ADHD). In this study, we investigated the association of recurrent genomic copy number variants (CNVs) with thoracic aortic aneurysms and dissections (TAAD). By using SNP arrays to screen and comparative genomic hybridization microarrays to validate, we identified 16p13.1 duplications in 8 out of 765 patients of European descent with adult-onset TAAD compared with 4 of 4,569 controls matched for ethnicity (P = 5.0×10−5, OR = 12.2). The findings were replicated in an independent cohort of 467 patients of European descent with TAAD (P = 0.005, OR = 14.7). Patients with 16p13.1 duplications were more likely to harbor a second rare CNV (P = 0.012) and to present with aortic dissections (P = 0.010) than patients without duplications. Duplications of 16p13.1 were identified in 2 of 130 patients with familial TAAD, but the duplications did not segregate with TAAD in the families. MYH11, a gene known to predispose to TAAD, lies in the duplicated region of 16p13.1, and increased MYH11 expression was found in aortic tissues from TAAD patients with 16p13.1 duplications compared with control aortas. These data suggest chromosome 16p13.1 duplications confer a risk for TAAD in addition to the established risk for neuropsychiatric disorders. It also indicates that recurrent CNVs may predispose to disorders involving more than one organ system, an observation critical to the understanding of the role of recurrent CNVs in human disease and a finding that may be common to other recurrent CNVs involving multiple genes

Genetic heterogeneity of the β-globin gene in various geographic populations of Yunnan in southwestern China.

The aim of this study was to investigate the geographic distribution of β-globin gene mutations in different ethnic groups in Yunnan province.From 2004 to 2014, 1,441 subjects with hemoglobin disorders, identified by PCR-reverse dot blot and DNA sequencing, were studied according to ethnicity and geographic origin. Haplotypes were examined among 41 unrelated thalassemia chromosomes.Eighteen β-thalassemia mutations and seven hemoglobin variants were identified for 1,616 alleles in 22 different ethnic groups from all 16 prefecture-level divisions of Yunnan. The prevalence of β-thalassemia was heterogeneous and regionally specific. CD 41-42 (-TCTT) was the most prevalent mutation in the populations of northeastern Yunnan. CD 17 (A>T) was the most common mutation in the populations of southeastern Yunnan, especially for the Zhuang minority, whereas Hb E (CD 26, G>A) was the most prevalent mutation in populations of southwestern Yunnan, especially for the Dai minority. Among the seven types of haplotypes identified, CD 17 (A>T) was mainly linked to haplotype VII (+ - - - - - +) and IVS-II-654 (C>T) was only linked to haplotype I (+ - - - - + +).Our data underline the heterogeneity of β-globin gene mutations in Yunnan. This distribution of β-globin mutations in the geographic regions and ethnic populations provided a detailed ethnic basis and evolutionary view of humans in southern China, which will be beneficial for genetic counseling and prevention strategies

Epidemiology characteristics of human coronaviruses in patients with respiratory infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010-2015 in Guangzhou.

Human coronavirus (HCoV) is one of the most common causes of respiratory tract infection throughout the world. To investigate the epidemiological and genetic variation of HCoV in Guangzhou, south China, we collected totally 13048 throat and nasal swab specimens from adults and children with fever and acute upper respiratory infection symptoms in Gunazhou, south China between July 2010 and June 2015, and the epidemiological features of HCoV and its species were studied. Specimens were screened for HCoV by real-time RT-PCR, and 7 other common respiratory viruses were tested simultaneously by PCR or real-time PCR. HCoV was detected in 294 cases (2.25%) of the 13048 samples, with most of them inpatients (251 cases, 85.4% of HCoV positive cases) and young children not in nursery (53.06%, 156 out of 294 HCoV positive cases). Four HCoVs, as OC43, 229E, NL63 and HKU1 were detected prevalent during 2010-2015 in Guangzhou, and among the HCoV positive cases, 60.20% were OC43, 16.67% were 229E, 14.97% were NL63 and 7.82% were HKU1. The month distribution showed that totally HCoV was prevalent in winter, but differences existed in different species. The 5 year distribution of HCoV showed a peak-valley distribution trend, with the detection rate higher in 2011 and 2013 whereas lower in 2010, 2012 and 2014. The age distribution revealed that children (especially those 50 years) were both high risk groups to be infected by HCoV. Of the 294 HCoV positive patients, 34.69% (101 cases) were co-infected by other common respiratory viruses, and influenza virus was the most common co-infecting virus (30/101, 29.70%). Fifteen HCoV-OC43 positive samples of 2013-2014 were selected for S gene sequencing and phylogenetic analysis, and the results showed that the 15 strains could be divided into 2 clusters in the phylogenetic tree, 12 strains of which formed a separate cluster that was closer to genotype G found in Malaysia. It was revealed for the first time that genotype B and genotype G of HCoV-OC43 co-circulated and the newly defined genotype G was epidemic as a dominant genotype during 2013-2014 in Guanzhou, south China

Frequency-specific age-related changes in the amplitude of spontaneous fluctuations in autism

Background: Autism spectrum disorder is characterized by atypical developmental changes during brain maturation, but regional brain functional changes that occur with age and across different frequency bands are unknown. Therefore, the current study aimed to explore potential age and frequency band-related changes in the regional brain activities in autism. Methods: A total of 65 participants who met the DSM-IV criteria for autistic disorder and 55 typically developed (TD) participants (both age 6-30 years) were recruited in the current study. The two groups were matched in age (t=-1.314, P=0.191) and gender (chi(2) =2.760, P=0.097). The amplitude of low-frequency fluctuations (ALFF) was employed to explore the effect of development on spontaneous brain activity in individuals with autism and in TD participants across slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), and slow-3 (0.073-0.1 Hz) frequency bands. The diagnosis-by-age interaction effect in the whole brain voxels in autism and TD groups was investigated. Results: Autism individuals showed significantly higher ALFF in the dorsal striatum in childhood (Caudate duster: t=3.626, P=0.001; Putamen cluster: t=2.839, P=0.007) and remarkably lower ALFF in the dorsal striatum in adulthood (Caudate cluster: t=-2.198, P=0.038; Putamen duster: t=-2.314, P=0.030) relative to TD, while no significant differences were observed in adolescence (all P>0.05). In addition, abnormal ALFF amplitudes were specific to the slow-4 (0.027-0.073 Hz) frequency band in the clusters above. Conclusions: The current study indicated abnormal development patterns in the spontaneous activity of the dorsal striatum in autism and highlighted the potential role of the slow-4 frequency band in the pathology of autism. Also, the potential brain mechanism of autism was revealed, suggesting that autism-related variations should be investigated in a specific frequency

The frequency of β-thalassemia mutations in different ethnic populations.

<p>^A: other 12 β-thalassemia mutations and 7 hemoglobin variants mutations;</p><p>^B: other minority ethnic groups, including Hani, Yao, Buyi, Naxi, Dong, Shui, Wa, Jinuo, Lafu, Khmer and Shan.</p><p>The frequency of β-thalassemia mutations in different ethnic populations.</p