Synteny of human chromosomes 14 and 15 in the platyrrhines (Primates, Platyrrhini)

In order to study the intra- and interspecific variability of the 14/15 association in Platyrrhini, we analyzed 15 species from 13 genera, including species that had not been described yet. The DNA libraries of human chromosomes 14 and 15 were hybridized to metaphases of Alouatta guariba clamitans, A. caraya, A. sara, Ateles paniscus chamek, Lagothrix lagothricha, Brachyteles arachnoides, Saguinus midas midas, Leontopithecus chrysomelas, Callimico goeldii, Callithrix sp., Cebus apella, Aotus nigriceps, Cacajao melanocephalus,Chiropotes satanas and Callicebus caligatus. The 14/15 hybridization pattern was present in 13 species, but not in Alouatta sara that showed a 14/15/14 pattern and Aotus nigriceps that showed a 15/14/15/14 pattern. In the majority of the species, the HSA 14 homologue retained synteny for the entire chromosome, whereas the HSA 15 homologue displayed fragmented segments. Within primates, the New World monkeys represent the taxon with the highest variability in chromosome number (2n = 16 to 62). The presence of the HSA 14/15 association in all species and subspecies studied herein confirms that this association is the ancestral condition for platyrrhines and that this association has been retained in most platyrrhines, despite the occurrence of extensive inter- and intrachromosomal rearrangements in this infraorder of Primates

Surtos de Crescimento de Manaus

There are few dynamic cities in the Amazon. Those that exist are located instrategic places for commercially commanding hinterlands or have privileged access to political resources. Manaus is exceptional in that it is a planned industrial city in the middle of Amazon rainforest, has a mestizo ethnic makeup and can be considered a success. However, the history of Manaus has experienced long periods of stagnation, intermittent surges of expansion and collapse. The legacy of a surge or surges in a city's historical constitutes an important way of identifying how it is different from others. Manaus passed through two distinct surges. After centuries of lack of demographic andeconomic growth, Manaus experienced the extraordinary rubber boom which lasted a couple of decades and was followed by collapse. Then, after decades of stagnation, in 1967 a second surge was induced by the Brazilian State. Based on industry this surge has achieved a degree of sustainability and is responsible for the present status of Manaus as a regional metropolis. Despite the lack of dynamism in previous centuries before these two surges Manaus had another important function, that of guaranteeing Portuguese possession of the vast Amazon basin which occupies the majority of the interior territories of South America.São poucas as cidades dinâmicas na Amazônia. As que existem o são, sobretudo, graças ao comércio associado a posições privilegiadas quanto à circulação e aos recursos a privilégios políticos, e a uma indústria moderna, no caso singular de Manaus. O modelo de Manaus uma cidade industrial planejada em meio à floresta e de marca cabocla pode ser considerado bem sucedido. Entretanto, sua história, registra surtos intermitentes que correspondem à expansão e colapso. O legado do surto - ou surtos -- vividos por uma cidade, é um fator importante a considerar na diferenciação das cidades. Manaus caracteriza-se por dois surtos bem marcados. Após longos séculos de ausência de crescimento, tanto de crescimento demográfico como econômico, dá-se um vertiginoso surto da borracha em poucas décadas, seguido de colapso. Encerrada a estagnação, novo surto se configura a partir de 1967, por iniciativa do Estado brasileiro. Baseado na indústria, revela certa sustentabilidade, respondendo pela posição atual da cidade como metrópole regional. A ausência de dinamismo através dos séculos revela, contudo, uma outra função cumprida nesse período: a de assegurar a posse por Portugal das terras amazônicas no interior da América do Sul.

Self Evaluation in the Selective Process for Full Professorship in the Department of Geography of the Federal University of Rio de Janeiro

This is the self-evaluation presented by Professor Bertha Koifmann Becker inDecember, 1993, when she was selected for the post of Full Professor at the Federal University of Rio de Janeiro. In this document she describes her academic and professional career, giving emphasis to her research, her role in strengthening the Department of Geography and her key part in founding the Post-graduate Program in Geography (PPGGIGEO/ UFRJ) as well as her significant contribution to different sectors of the Brazilian government, innumerous national and international universities and research institutes, always offering rich, spontaneous and brilliant scientific insight. At the end of the text a résumé is added, presenting the professional accomplishments and numerous national and international prizes and medals received by one of the greatest Brazilian geographers. O material aqui apresentado corresponde ao corpo do texto do Memorial apresentadopela Profa. Bertha Koiffmann Becker em Dezembro de 1993, por ocasião do concursorealizado para provimento do Cargo de professor Titular da Universidade Federal do Rio de Janeiro. Nele consta seu relato sobre sua importante trajetória acadêmico-profissional,ressaltando, principalmente, as temáticas abordadas em suas pesquisas, seu papel no fortalecimentodo Departamento de Geografia da UFRJ e sua significativa contribuição naimplantação e dinamização do Programa de Pós-Graduação em Geografia (PPGG-IGEO/UFRJ), além de sua valiosa participação em setores do governo brasileiro e em inúmeras Universidades, Institutos e Organizações de Ensino e Pesquisa Nacionais e Internacionais, contribuindo de forma sempre rica, espontânea e, podemos dizer, brilhante à Ciência! Ao final de seu relato fizemos uma síntese de sua atuação profissional e suas inúmeras premiaçõese condecorações, demonstrando a salutar contribuição a Ciência de uma das mais preciosas Geógrafas brasileira que teve reconhecimento mundial

Copy Number Variants in Obesity-Related Syndromes: Review and Perspectives on Novel Molecular Approaches

In recent decades, obesity has reached epidemic proportions worldwide and became a major concern in public health. Despite heritability estimates of 40 to 70% and the long-recognized genetic basis of obesity in a number of rare cases, the list of common obesity susceptibility variants by the currently published genome-wide association studies (GWASs) only explain a small proportion of the individual variation in risk of obesity. It was not until very recently that GWASs of copy number variants (CNVs) in individuals with extreme phenotypes reported a number of large and rare CNVs conferring high risk to obesity, and specifically deletions on chromosome 16p11.2. In this paper, we comment on the recent advances in the field of genetics of obesity with an emphasis on the genes and genomic regions implicated in highly penetrant forms of obesity associated with developmental disorders. Array genomic hybridization in this patient population has afforded discovery opportunities for CNVs that have not previously been detectable. This information can be used to generate new diagnostic arrays and sequencing platforms, which will likely enhance detection of known genetic conditions with the potential to elucidate new disease genes and ultimately help in developing a next-generation sequencing protocol relevant to clinical practice

A family case of fertile human 45,X,psu dic(15;Y) males

We report on a familial case including four male probands from three generations with a 45,X,psu dic(15;Y)(p11.2;q12) karyotype. 45,X is usually associated with a female phenotype and only rarely with maleness, due to translocation of small Y chromosomal fragments to autosomes. These male patients are commonly infertile because of missing azoospermia factor regions from the Y long arm. In our familial case we found a pseudodicentric translocation chromosome, that contains almost the entire chromosomes 15 and Y. The translocation took place in an unknown male ancestor of our probands and has no apparent effect on fertility and phenotype of the carrier. FISH analysis demonstrated the deletion of the pseudoautosomal region 2 (PAR2) from the Y chromosome and the loss of the nucleolus organizing region (NOR) from chromosome 15. The formation of the psu dic(15;Y) chromosome is a reciprocal event to the formation of the satellited Y chromosome (Yqs). Statistically, the formation of 45,X,psu dic(15;Y) (p11.2;q12) is as likely as the formation of Yqs. Nevertheless, it has not been described yet. This can be explained by the dicentricity of this translocation chromosome that usually leads to mitotic instability and meiotic imbalances. A second event, a stable inactivation of one of the two centromeres is obligatory to enable the transmission of the translocation chromosome and thus a stably reduced chromosome number from father to every son in this family

Investigation of selected genomic deletions and duplications in a cohort of 338 patients presenting with syndromic obesity by multiplex ligation-dependent probe amplification using synthetic probes

Background: Certain rare syndromes with developmental delay or intellectual disability caused by genomic copy number variants (CNVs), either deletions or duplications, are associated with higher rates of obesity. Current strategies to diagnose these syndromes typically rely on phenotype-driven investigation. However, the strong phenotypic overlap between syndromic forms of obesity poses challenges to accurate diagnosis, and many different individual cytogenetic and molecular approaches may be required. Multiplex ligation-dependent probe amplification (MLPA) enables the simultaneous analysis of multiple targeted loci in a single test, and serves as an important screening tool for large cohorts of patients in whom deletions and duplications involving specific loci are suspected. Our aim was to design a synthetic probe set for MLPA analysis to investigate in a cohort of 338 patients with syndromic obesity deletions and duplications in genomic regions that can cause this phenotype.Results: We identified 18 patients harboring copy number imbalances; 18 deletions and 5 duplications. the alterations in ten patients were delineated by chromosomal microarrays, and in the remaining cases by additional MLPA probes incorporated into commercial kits. Nine patients showed deletions in regions of known microdeletion syndromes with obesity as a clinical feature: in 2q37 (4 cases), 9q34 (1 case) and 17p11.2 (4 cases). Four patients harbored CNVs in the DiGeorge syndrome locus at 22q11.2. Two other patients had deletions within the 22q11.2 'distal' locus associated with a variable clinical phenotype and obesity in some individuals. the other three patients had a recurrent CNV of one of three susceptibility loci: at 1q21.1 'distal', 16p11.2 'distal', and 16p11.2 'proximal'.Conclusions: Our study demonstrates the utility of an MLPA-based first line screening test to the evaluation of obese patients presenting with syndromic features. the overall detection rate with the synthetic MLPA probe set was about 5.3% (18 out of 338). Our experience leads us to suggest that MLPA could serve as an effective alternative first line screening test to chromosomal microarrays for diagnosis of syndromic obesity, allowing for a number of loci (e.g., 1p36, 2p25, 2q37, 6q16, 9q34, 11p14, 16p11.2, 17p11.2), known to be clinically relevant for this patient population, to be interrogated simultaneously.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Human Genome & Stem Cell Ctr, São Paulo, BrazilUniv São Paulo, Sch Med, Children Inst, Genet Unit,Dept Pediat, São Paulo, BrazilUniv São Paulo, Sch Med, Dept Med Genet, Neurogenet Unit, BR-14049 Ribeirao Preto, BrazilUniversidade Federal de São Paulo, Ctr Med Genet, Dept Morphol, São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Med Genet, Dept Morphol, São Paulo, BrazilFAPESP: 09/52523-1FAPESP: 1998/14254-2CNPq: 304381/2007-1Web of Scienc

Paternal UPD15: Further Genetic and Clinical Studies in Four Angelman Syndrome Patients

Among 25 patients diagnosed with Angelman syndrome, we detected 21 with deletion and 4 with paternal uniparental disomy (UPD), 2 isodisomies originating by postzygotic error, and 1 MII nondisjunction event. The diagnosis was obtained by molecular techniques, including methylation pattern analysis of exon 1 of SNRPN and microsatellite analysis of loci within and outside the 15q11-q13 region. Most manifestations present in deletion patients are those previously reported. Comparing the clinical data from our and published UPD patients with those with deletions we observed the following: the age of diagnosis is higher in UPD group (average 7 3 ⁄12 years), microcephaly is more frequent among deletion patients, UPD children start walking earlier (average age 2 9 ⁄12 years), whereas in deletion patients the average is 4 1 ⁄2 years, epilepsy started later in UPD patients (average 5 10 ⁄12 years) than in deletion patients (average 1 11 ⁄12 years), weight above the 75th centile is reported mainly in UPD patients, complete absence of speech is more common in the deleted (88.9%) than in the UPD patients because half of the children are able to say few words. Thus, besides the abnormalities already described, the UPD patients have somewhat better verbal development, a weight above the 75th centile, and OFC in the upper normal range. Am. J. Med. Genet. 92:322-327, 2000

A clinical follow-up of 35 Brazilian patients with Prader-Willi Syndrome

OBJECTIVE: Prader-Willi Syndrome is a common etiology of syndromic obesity that is typically caused by either a paternal microdeletion of a region in chromosome 15 (microdeletions) or a maternal uniparental disomy of this chromosome. The purpose of this study was to describe the most significant clinical features of 35 Brazilian patients with molecularly confirmed Prader-Willi syndrome and to determine the effects of growth hormone treatment on clinical outcomes. METHODS: A retrospective study was performed based on the medical records of a cohort of 35 patients diagnosed with Prader-Willi syndrome. The main clinical characteristics were compared between the group of patients presenting with microdeletions and the group presenting with maternal uniparental disomy of chromosome 15. Curves for height/length, weight and body mass index were constructed and compared between Prader-Willi syndrome patients treated with and without growth hormone to determine how growth hormone treatment affected body composition. The curves for these patient groups were also compared with curves for the normal population. RESULTS: No significant differences were identified between patients with microdeletions and patients with maternal uniparental disomy for any of the clinical parameters measured. Growth hormone treatment considerably improved the control of weight gain and body mass index for female patients but had no effect on either parameter in male patients. Growth hormone treatment did not affect height/length in either gender. CONCLUSION: The prevalence rates of several clinical features in this study are in agreement with the rates reported in the literature. Additionally, we found modest benefits of growth hormone treatment but failed to demonstrate differences between patients with microdeletions and those with maternal uniparental disomy. The control of weight gain in patients with Prader-Willi syndrome is complex and does not depend exclusively on growth hormone treatment