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NEK1 variants confer susceptibility to amyotrophic lateral sclerosis

Kenna, Kevin P. (author)
van Doormaal, Perry T. C. (author)
Dekker, Annelot M. (author)
show more...
Ticozzi, Nicola (author)
Kenna, Brendan J. (author)
Diekstra, Frank P. (author)
van Rheenen, Wouter (author)
van Eijk, Kristel R. (author)
Jones, Ashley R. (author)
Keaglel, Pamela (author)
Shatunov, Aleksey (author)
Sproviero, William (author)
Smiths, Bradley N. (author)
van Es, Michael A. (author)
Topps, Simon D. (author)
Kenna, Aoife (author)
Miller, Jack W. (author)
Fallini, Claudia (author)
Tiloca, Cinzia (author)
McLaughlin, Russell L. (author)
Vance, Caroline (author)
Troakes, Claire (author)
Colombrita, Claudia (author)
Mora, Gabriele (author)
Calvo, Andrea (author)
Verde, Federico (author)
Al-Sarraj, Safa (author)
King, Andrew (author)
Calini, Daniela (author)
de Belleroche, Jacqueline (author)
Baas, Frank (author)
van der Kooi, Anneke J. (author)
de Visser, Marianne (author)
ten Asbroek, Anneloor L. M. A. (author)
Sapp, Peter C. (author)
McKenna-Yasek, Diane (author)
Polak, Meraida (author)
Asress, Seneshaw (author)
Luis Munoz-Blanco, Jose (author)
Strom, Tim M. (author)
Meitinger, Thomas (author)
Morrison, Karen E. (author)
Lauria, Giuseppe (author)
Williams, Kelly L. (author)
Leigh, P. Nigel (author)
Nicholson, Garth A. (author)
Blair, Ian P. (author)
Leblond, Claire S. (author)
Dion, Patrick A. (author)
Rouleau, Guy A. (author)
Pall, Hardev (author)
Shaw, Pamela J. (author)
Turner, Martin R. (author)
Talbot, Kevin (author)
Taroni, Franco (author)
Boylan, Kevin B. (author)
Van Blitterswijk, Marka (author)
Rademakers, Rosa (author)
Esteban-Perez, Jesus (author)
Garcia-Redondo, Alberto (author)
Van Damme, Phillip (author)
Robberecht, Wim (author)
Chio, Adrian (author)
Gellera, Cinzia (author)
Drepper, Carsten (author)
Sendtner, Michael (author)
Ratti, Antonia (author)
Glass, Jonathan D. (author)
Mora, Jesus S. (author)
Basak, Nazli A. (author)
Hardiman, Orla (author)
Ludolph, Albert C. (author)
Andersen, Peter M. (author)
Umeå universitet,Klinisk neurovetenskap
Weishaupt, Jochen H. (author)
Brown, Robert H., Jr. (author)
Al-Chalabi, Ammar (author)
Silani, Vincenzo (author)
Shaw, Christopher E. (author)
van den Berg, Leonard H. (author)
Veldink, Jan H. (author)
Landers, John E. (author)
D'Alfonso, Sandra (author)
Mazzini, Letizia (author)
Comi, Giacomo P. (author)
Del Bo, Roberto (author)
Ceroni, Mauro (author)
Gagliardi, Stella (author)
Querin, Giorgia (author)
Bertolin, Cinzia (author)
Pensato, Viviana (author)
Castellotti, Barbara (author)
Corti, Stefania (author)
Cereda, Cristina (author)
Corrado, Lucia (author)
Soraru, Gianni (author)
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 (creator_code:org_t)
2016-07-25
2016
English.
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1037-1042
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261 His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261 His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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ref (subject category)
art (subject category)

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By the author/editor
Kenna, Kevin P.
van Doormaal, Pe ...
Dekker, Annelot ...
Ticozzi, Nicola
Kenna, Brendan J ...
Diekstra, Frank ...
show more...
van Rheenen, Wou ...
van Eijk, Kriste ...
Jones, Ashley R.
Keaglel, Pamela
Shatunov, Alekse ...
Sproviero, Willi ...
Smiths, Bradley ...
van Es, Michael ...
Topps, Simon D.
Kenna, Aoife
Miller, Jack W.
Fallini, Claudia
Tiloca, Cinzia
McLaughlin, Russ ...
Vance, Caroline
Troakes, Claire
Colombrita, Clau ...
Mora, Gabriele
Calvo, Andrea
Verde, Federico
Al-Sarraj, Safa
King, Andrew
Calini, Daniela
de Belleroche, J ...
Baas, Frank
van der Kooi, An ...
de Visser, Maria ...
ten Asbroek, Ann ...
Sapp, Peter C.
McKenna-Yasek, D ...
Polak, Meraida
Asress, Seneshaw
Luis Munoz-Blanc ...
Strom, Tim M.
Meitinger, Thoma ...
Morrison, Karen ...
Lauria, Giuseppe
Williams, Kelly ...
Leigh, P. Nigel
Nicholson, Garth ...
Blair, Ian P.
Leblond, Claire ...
Dion, Patrick A.
Rouleau, Guy A.
Pall, Hardev
Shaw, Pamela J.
Turner, Martin R ...
Talbot, Kevin
Taroni, Franco
Boylan, Kevin B.
Van Blitterswijk ...
Rademakers, Rosa
Esteban-Perez, J ...
Garcia-Redondo, ...
Van Damme, Phill ...
Robberecht, Wim
Chio, Adrian
Gellera, Cinzia
Drepper, Carsten
Sendtner, Michae ...
Ratti, Antonia
Glass, Jonathan ...
Mora, Jesus S.
Basak, Nazli A.
Hardiman, Orla
Ludolph, Albert ...
Andersen, Peter ...
Weishaupt, Joche ...
Brown, Robert H. ...
Al-Chalabi, Amma ...
Silani, Vincenzo
Shaw, Christophe ...
van den Berg, Le ...
Veldink, Jan H.
Landers, John E.
D'Alfonso, Sandr ...
Mazzini, Letizia
Comi, Giacomo P.
Del Bo, Roberto
Ceroni, Mauro
Gagliardi, Stell ...
Querin, Giorgia
Bertolin, Cinzia
Pensato, Viviana
Castellotti, Bar ...
Corti, Stefania
Cereda, Cristina
Corrado, Lucia
Soraru, Gianni
show less...
About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Medical Genetics
Articles in the publication
Nature Genetics
By the university
Umeå University

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