Browsing by Subject "phenotype"

Now showing 1 - 6 of 6

Open Access
The bonobo genome compared with the chimpanzee and human genomes
(2012) Prüfer, K.; Munch, K.; Hellmann I.; Akagi, K.; Miller J.R.; Walenz, B.; Koren, S.; Sutton G.; Kodira, C.; Winer, R.; Knight J.R.; Mullikin J.C.; Meader, S.J.; Ponting, C.P.; Lunter G.; Higashino, S.; Hobolth, A.; Dutheil J.; Karakoç, E.; Alkan, C.; Sajjadian, S.; Catacchio, C.R.; Ventura, M.; Marques-Bonet, T.; Eichler, E.E.; André, C.; Atencia, R.; Mugisha L.; Junhold J.; Patterson, N.; Siebauer, M.; Good J.M.; Fischer, A.; Ptak, S.E.; Lachmann, M.; Symer, D.E.; Mailund, T.; Schierup, M.H.; Andrés, A.M.; Kelso J.; Pääbo, S.
Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other. © 2012 Macmillan Publishers Limited. All rights reserved.
Open Access
The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity
(Nature Publishing Group, 2015) Sag, D.; Cekic, C.; Wu, R.; Linden J.; Hedrick, C.C.
ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1-/- mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1-/- mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1-/- macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer. © 2015 Macmillan Publishers Limited. All rights reserved.
Open Access
Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies
(Elsevier Ltd, 2014) Kayman-Kurekci G.; Talim, B.; Korkusuz P.; Sayar, N.; Sarioglu, T.; Oncel I.; Sharafi P.; Gundesli H.; Balci-Hayta, B.; Purali, N.; Serdaroglu-Oflazer P.; Topaloglu H.; Dincer P.
We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, rigid spine and contractures of the proximal and distal interphalangeal hand joints. Additionally, cardiomyopathy and respiratory involvement were noted. DNA sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina-associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We observed that expression of LAP1B was absent in the patient skeletal muscle fibres. Ultrastructural examination showed intact sarcomeric organization but alterations of the nuclear envelope including nuclear fragmentation, chromatin bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein localized in the inner nuclear membrane that binds to both A- and B-type lamins, and is involved in the regulation of torsinA ATPase. Interestingly, luminal domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA-was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the findings suggest that LAP1 and LULL1 might have a compensatory effect on each other. This study expands the spectrum of genes associated with nuclear envelopathies and highlights the critical function for LAP1B in striated muscle. © 2014 Elsevier B.V.
Open Access
Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans
(National Academy of Sciences, 2008) Ozcelik, T.; Akarsu, N.; Uz, E.; Caglayan, S.; Gulsuner, S.; Onat, O. E.; Tan, M.; Tan, U.
Quadrupedal gait in humans, also known as Unertan syndrome, is a rare phenotype associated with dysarthric speech, mental retardation, and varying degrees of cerebrocerebellar hypoplasia. Four large consanguineous kindreds from Turkey manifest this phenotype. In two families (A and D), shared homozygosity among affected relatives mapped the trait to a 1.3-Mb region of chromosome 9p24. This genomic region includes the VLDLR gene, which encodes the very low-density lipoprotein receptor, a component of the reelin signaling pathway involved in neuroblast migration in the cerebral cortex and cerebellum. Sequence analysis of VLDLR revealed nonsense mutation R257X in family A and single-nucleotide deletion c2339delT in family D. Both these mutations are predicted to lead to truncated proteins lacking transmembrane and signaling domains. In two other families (B and C), the phenotype is not linked to chromosome 9p. Our data indicate that mutations in VLDLR impair cerebrocerebellar function, conferring in these families a dramatic influence on gait, and that hereditary disorders associated with quadrupedal gait in humans are genetically heterogeneous.
Open Access
De novo balanced (X;14) translocation in a patient with recurrent miscarriages: Case report
(2011) Alpaslan Pinarli F.; Ökten G.; ÖzçelIk, T.; Kara, N.; Güneş, S.; Koçak I.
We report a 23-year-old phenotypically normal female patient who had previously suffered from recurrent spontaneous abortion (RSA) who found to have an X;14 trans location and a Methylene- Tetrahdrofolate-Reductase (MTHFR) C677T heterozygote mutation. G-banding cytogenetic analysis was cultured from the peripheral blood lymphocy tes. MTHFR, factor V Leiden and prothrombin gene mutations were studied from DNA obtained from peripheral blood lym- phocytes with stripassay. DNA for X inactivation pattern study was also obtained with the method described above. G-banding cytogentic analysis from cultured peripheral blood lymphocytes of the patient revealed 46,XderX,t(X;14)(q13;q32) and found to be heterozygous for C677T MTHFR mutation. An X inactivation pattern study revealed a complete inactivated nor mal X chromosome, asexpected. The possible causes of recurrent miscarriages in our patient were unbalanced gametes, skewed X inactivation and MTHFR C677T heterozygote mutation. © 2011 by Türkiye Klinikleri.
Open Access
Systematic discovery of Rab GTPases with synaptic functions in Drosophila
(2011) Chan, C.-C.; Scoggin, S.; Wang, D.; Cherry, S.; Dembo, T.; Greenberg, B.; Jin, E.J.; Kuey, C.; Lopez, A.; Mehta, S.Q.; Perkins, T.J.; Brankatschk, M.; Rothenfluh, A.; Buszczak, M.; Hiesinger P.R.
Background: Neurons require highly specialized intracellular membrane trafficking, especially at synapses. Rab GTPases are considered master regulators of membrane trafficking in all cells, and only very few Rabs have known neuron-specific functions. Here, we present the first systematic characterization of neuronal expression, subcellular localization, and function of Rab GTPases in an organism with a brain. Results: We report the surprising discovery that half of all Drosophila Rabs function specifically or predominantly in distinct subsets of neurons in the brain. Furthermore, functional profiling of the GTP/GDP-bound states reveals that these neuronal Rabs are almost exclusively active at synapses and the majority of these synaptic Rabs specifically mark synaptic recycling endosomal compartments. Our profiling strategy is based on Gal4 knockins in large genomic fragments that are additionally designed to generate mutants by ends-out homologous recombination. We generated 36 large genomic targeting vectors and transgenic rab-Gal4 fly strains for 25 rab genes. Proof-of-principle knockout of the synaptic rab27 reveals a sleep phenotype that matches its cell-specific expression. Conclusions: Our findings suggest that up to half of all Drosophila Rabs exert specialized synaptic functions. The tools presented here allow systematic functional studies of these Rabs and provide a method that is applicable to any large gene family in Drosophila. © 2011 Elsevier Ltd. All rights reserved.