Li, Z; Peng, Y; Hufnagel, RB; Hu, YC; Zhao, C; Queme, LF; Khuchua, Z; Driver, AM; Dong, F; Lu, QR; Lindquist, DM; Jankowski, MP; Stottmann, RW; Kao, WWY; Huang, T. Loss of SLC25A46 causes neurodegeneration by affecting mitochondrial dynamics and energy production in mice. Human Molecular Genetics. 2017; 26(19):3776-3791.
Biallelic mutations of SLC25A46 in patients with multiple neuropathies. The cellular basis and pathogenic mechanism of the SLC25A46-related neuropathies were not however previously known. This study revealed that mutant mice showed impaired electron transport chain activity and accumulated autophagy markers. These findings indicate loss of SLC25A46 causes degeneration in neurons by affecting mitochondrial dynamics and energy production.
DiStasio, A; Driver, A; Sund, K; Donlin, M; Muraleedharan, RM; Pooya, S; Kline-Fath, B; Kaufman, KM; Prows, CA; Schorry, E; Dasgupta, B; Stottmann, RW. Copb2 is essential for embryogenesis and hypomorphic mutations cause human microcephaly. Human Molecular Genetics. 2017; 26(24):4836-4848.
Primary microcephaly is a congenital brain malformation with a very small head circumference and moderate to severe mental deficiencies . Recent exome sequencing revealed an autosomal recessive mutation leading to an amino acid substitution in a WD40 domain of the highly conserved Coatomer Protein Complex, Subunit Beta 2 (COPB2). To study the role of Copb2 in neural development, the Stottman laboratory utilized genome-editing technology to generate an allelic series in mice demonstrating that Copb2 is essential for early stages of embryogenesis.
Mitteroecker, P; Windhager, S; Pavlicev, M. Cliff-edge model predicts intergenerational predisposition to dystocia and Caesarean delivery. Proceedings of the National Academy of Sciences of the United States of America. 2017; 114(44):11669-11672.
According to the cliff-edge model, the routine use caesarean sections since the mid-20th century has promoted an evolutionary increase of fetal size relative to the dimensions of the maternal birth canal with resulting complications in child birth. Use of multigenerational epidemiological studies support this intergenerational predisposition to requiring surgical delivery. These findings suggest report risks for caesarean up to twice as high for women born by caesarean compared with women born vaginally.
Martin, LJ; He, H; Collins, MH; Abonia, JP; Biagini Myers, JM; Eby, M; Johansson, H; Kottyan, LC; Khurana Hershey, GK; Rothenberg, ME. Eosinophilic esophagitis (EoE) genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci. Journal of Allergy and Clinical Immunology. 2018; 141(5):1690-1698.
This is an excellent example of important team science that mediated risk of EoE is EoE-specific and general atopic disease loci, which can have interactive effects. These results might aid in identifying potential therapeutics and predicting EoE susceptibility.
Lesmana, H; Dyer, L; Li, X; Denton, J; Griffiths, J; Chonat, S; Seu, KG; Heeney, MM; Zhang, K; Hopkin, RJ; Kalfa, TA. Alu element insertion in PKLR gene as a novel cause of pyruvate kinase deficiency in Middle Eastern patients. Human Mutation. 2018; 39(3):389-393.
This paper reveals a new mechanism in causing pyruvate kinase deficiency.