Human Genetics Program

José Luis Millán, Ph.D. and young patient

Gene effects

Most genetic disorders are present from birth and are quite rare, often affecting only one person in every several thousand or million.

While some of these genetic diseases are well known, such as sickle cell anemia and cystic fibrosis, others are so rare that there is only one affected person in the world. Whether a genetic disease affects thousands or just one person, there are many challenges for patients, their families, and caregivers, including the time it takes for many patients to get a correct diagnosis. 

Director's statement

Our focus is on the discovery of new genetic disorders and improving our understanding of those we already know. Using zebrafish, mouse models, patient cells and stem cell technologies, we are probing the pathological mechanisms of genetic disorders to address unanswered questions. Our fundamental research has led to clinically useful diagnostic tests and novel therapies for patients. Strong patient and advocacy relations serve as a foundation for our goal to shed light on the obscure paths of genetic disorders and provide solid information and guidance.

– Hudson Freeze, Ph.D., Program Director

Appointments

Publications

Inhibition of Tissue-Nonspecific Alkaline Phosphatase Attenuates Ectopic Mineralization in the Abcc6-/- Mouse Model of PXE but Not in the Enpp1 Mutant Mouse Models of GACI.

Li Q, Huang J, Pinkerton AB, Millan JL, van Zelst BD, Levine MA, Sundberg JP, Uitto J

J Invest Dermatol 2019 Feb ;139(2):360-368

A mammalian homolog of the zebrafish transmembrane protein 2 (TMEM2) is the long-sought-after cell-surface hyaluronidase.

Yamamoto H, Tobisawa Y, Inubushi T, Irie F, Ohyama C, Yamaguchi Y

J Biol Chem 2017 May 5 ;292(18):7304-7313

A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome, Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation.

Ferreira CR, Xia ZJ, Clément A, Parry DA, Davids M, Taylan F, Sharma P, Turgeon CT, Blanco-Sánchez B, Ng BG, Logan CV, Wolfe LA, Solomon BD, Cho MT, Douglas G, Carvalho DR, Bratke H, Haug MG, Phillips JB, Wegner J, Tiemeyer M, Aoki K, Undiagnosed Diseases Network., Scottish Genome Partnership., Nordgren A, Hammarsjö A, Duker AL, Rohena L, Hove HB, Ek J, Adams D, Tifft CJ, Onyekweli T, Weixel T, Macnamara E, Radtke K, Powis Z, Earl D, Gabriel M, Russi AHS, Brick L, Kozenko M, Tham E, Raymond KM, Phillips JA 3rd, Tiller GE, Wilson WG, Hamid R, Malicdan MCV, Nishimura G, Grigelioniene G, Jackson A, Westerfield M, Bober MB, Gahl WA, Freeze HH

Am J Hum Genet 2018 Oct 4 ;103(4):553-567

Origin of cytoplasmic GDP-fucose determines its contribution to glycosylation reactions.

Sosicka P, Ng BG, Pepi LE, Shajahan A, Wong M, Scott DA, Matsumoto K, Xia ZJ, Lebrilla CB, Haltiwanger RS, Azadi P, Freeze HH

J Cell Biol 2022 Oct 3 ;221(10)

A recurrent homozygous missense DPM3 variant leads to muscle and brain disease.

Nagy S, Lau T, Alavi S, Karimiani EG, Vallian J, Ng BG, Noroozi Asl S, Akhondian J, Bahreini A, Yaghini O, Uapinyoying P, Bonnemann C, Freeze HH, Dissanayake VHW, Sirisena ND, Schmidts M, Houlden H, Moreno-De-Luca A, Maroofian R

Clin Genet 2022 Aug 6 ;

The cell surface hyaluronidase TMEM2 plays an essential role in mouse neural crest cell development and survival.

Inubushi T, Nakanishi Y, Abe M, Takahata Y, Nishimura R, Kurosaka H, Irie F, Yamashiro T, Yamaguchi Y

PLoS Genet 2022 Jul ;18(7):e1009765

Clinical, biochemical and genetic characteristics of MOGS-CDG: a rare congenital disorder of glycosylation.

Shimada S, Ng BG, White AL, Nickander KK, Turgeon C, Liedtke KL, Lam CT, Font-Montgomery E, Lourenco CM, He M, Peck DS, Umana LA, Uhles CL, Haynes D, Wheeler PG, Bamshad MJ, Nickerson DA, Cushing T, Gates R, Gomez-Ospina N, Byers HM, UW Center for Mendelian Genomics., Scalco FB, Martinez NN, Sachdev R, Smith L, Poduri A, Malone S, Harris RV, Scheffer IE, Rosenzweig SD, Adams DR, Gahl WA, Malicdan MCV, Raymond KM, Freeze HH, Wolfe LA

J Med Genet 2022 Jul 5 ;

CAMLG-CDG: a novel congenital disorder of glycosylation linked to defective membrane trafficking.

Wilson MP, Durin Z, Unal Ö, Ng BG, Marrecau T, Keldermans L, Souche E, Rymen D, Gündüz M, Köse G, Sturiale L, Garozzo D, Freeze HH, Jaeken J, Foulquier F, Matthijs G

Hum Mol Genet 2022 Aug 17 ;31(15):2571-2581

Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish.

Ai X, Ye Z, Xiao C, Zhong J, Lancman JJ, Chen X, Pan X, Yang Y, Zhou L, Wang X, Shi H, Zhang D, Yao Y, Cao D, Zhao C

Dis Model Mech 2022 Apr 1 ;15(4)

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