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



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

Liver Involvement in Congenital Disorders of Glycosylation. A Systematic Review.

Colantuono R, D'Acunto E, Melis D, Vajro P, Freeze HH, Mandato C

J Pediatr Gastroenterol Nutr 2021 Jun 24 ;

A mutation in SLC37A4 causes a dominantly inherited congenital disorder of glycosylation characterized by liver dysfunction.

Ng BG, Sosicka P, Fenaille F, Harroche A, Vuillaumier-Barrot S, Porterfield M, Xia ZJ, Wagner S, Bamshad MJ, Vergnes-Boiteux MC, Cholet S, Dalton S, Dell A, Dupré T, Fiore M, Haslam SM, Huguenin Y, Kumagai T, Kulik M, McGoogan K, Michot C, Nickerson DA, Pascreau T, Borgel D, Raymond K, Warad D, University of Washington Center for Mendelian Genomics (UW-CMG)., Flanagan-Steet H, Steet R, Tiemeyer M, Seta N, Bruneel A, Freeze HH

Am J Hum Genet 2021 Jun 3 ;108(6):1040-1052

ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes.

Alsharhan H, He M, Edmondson AC, Daniel EJP, Chen J, Donald T, Bakhtiari S, Amor DJ, Jones EA, Vassallo G, Vincent M, Cogné B, Deb W, Werners AH, Jin SC, Bilguvar K, Christodoulou J, Webster RI, Yearwood KR, Ng BG, Freeze HH, Kruer MC, Li D, Raymond KM, Bhoj EJ, Sobering AK

J Inherit Metab Dis 2021 Mar 18 ;

The Cell Surface Hyaluronidase TMEM2 Regulates Cell Adhesion and Migration via Degradation of Hyaluronan at Focal Adhesion Sites.

Irie F, Tobisawa Y, Murao A, Yamamoto H, Ohyama C, Yamaguchi Y

J Biol Chem 2021 Feb 26 ;:100481

Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study.

Witters P, Edmondson AC, Lam C, Johnsen C, Patterson MC, Raymond KM, He M, Freeze HH, Morava E

Orphanet J Rare Dis 2021 Feb 25 ;16(1):102

Expanding the phenotype, genotype and biochemical knowledge of ALG3-CDG.

Alsharhan H, Ng BG, Daniel EJP, Friedman J, Pivnick EK, Al-Hashem A, Faqeih EA, Liu P, Engelhardt NM, Keller KN, Chen J, Mazzeo PA, University of Washington Center for Mendelian Genomics (UW-CMG)., Rosenfeld JA, Bamshad MJ, Nickerson DA, Raymond KM, Freeze HH, He M, Edmondson AC, Lam C

J Inherit Metab Dis 2021 Feb 13 ;

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