Journal of Genetics and Genomics

Genetics of anorexia nervosa: An overview of genome-wide association studies and emerging biological links

Clara de Jorge Martínez, Gull Rukh, Michael J. Williams, Santino Gaudio, Samantha Brooks, Helgi B. Schiöth

2022, 49(1): 1-12. doi: 10.1016/j.jgg.2021.09.005

Abstract (363) PDF (45)

Abstract:
Anorexia nervosa (AN) is a complex disorder with a strong genetic component. Comorbidities are frequent and there is substantial overlap with other disorders. The lack of understanding of the molecular and neuroanatomical causes has made it difficult to develop effective treatments and it is often difficult to treat in clinical practice. Recent advances in genetics have changed our understanding of polygenic diseases, increasing the possibility of understanding better how molecular pathways are intertwined. This review synthetizes the current state of genetic research providing an overview of genome-wide association studies (GWAS) findings in AN as well as overlap with other disorders, traits, pathways, and imaging results. This paper also discusses the different putative global pathways that are contributing to the disease including the evidence for metabolic and psychiatric origin of the disease.

Newborn screening with targeted sequencing: a multicenter investigation and a pilot clinical study in China

Chanjuan Hao, Ruolan Guo, Xuyun Hu, Zhan Qi, Qi Guo, Xuanshi Liu, Yuanhu Liu, Yanhua Sun, Xiaofen Zhang, Feng Jin, Xiujie Wu, Ren Cai, Dingyuan Zeng, Xijiang Hu, Xiaohua Wang, Xiaoping Ji, Wenjie Li, Quansheng Xing, Lanfang Mu, Xiulian Jiang, Xue Yang, Weimin Yang, Yan Zhang, Qianli Yin, Xin Ni, Wei Li

2022, 49(1): 13-19. doi: 10.1016/j.jgg.2021.08.008

Abstract (396) PDF (41)

Abstract:
Different newborn screening (NBS) programs have been practiced in many countries since the 1960s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing (NESTS) program to screen 11,484 babies in 8 Women and Children's hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85% (902/11,484). With 45.89% (414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07% (50/414), estimating an average of 0.95% (7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.

G-quadruplexes in genomes of viruses infecting eukaryotes or prokaryotes are under different selection pressures from hosts

Zhen Li, Sheng Hu Qian, Fan Wang, Hany I. Mohamed, Guangfu Yang, Zhen-Xia Chen, Dengguo Wei

2022, 49(1): 20-29. doi: 10.1016/j.jgg.2021.08.018

Abstract (213) PDF (13)

Abstract:
G-quadruplexes in viral genomes can be applied as the targets of antiviral therapies, which has attracted wide interest. However, it is still not clear whether the pervasive number of such elements in the viral world is the result of natural selection for functionality. In this study, we identified putative quadruplex-forming sequences (PQSs) across the known viral genomes and analyzed the abundance, structural stability, and conservation of viral PQSs. A Viral Putative G-quadruplex Database (http://jsjds.hzau.edu.cn/MBPC/ViPGD/index.php/home/index) was constructed to collect the details of each viral PQS, which provides guidance for selecting the desirable PQS. The PQS with two putative G-tetrads (G₂-PQS) was significantly enriched in both eukaryotic viruses and prokaryotic viruses, whereas the PQSs with three putative G-tetrads (G₃-PQS) were only enriched in eukaryotic viruses and depleted in prokaryotic viruses. The structural stability of PQSs in prokaryotic viruses was significantly lower than that in eukaryotic viruses. Conservation analysis showed that the G₂-PQS, instead of G₃-PQS, was highly conserved within the genus. This suggested that the G₂-quadruplex might play an important role in viral biology, and the difference in the occurrence of G-quadruplex between eukaryotic viruses and prokaryotic viruses may result from the different selection pressures from hosts.

Nucleolar histone deacetylases HDT1, HDT2, and HDT3 regulate plant reproductive development

Yu Luo, Dong-Qiao Shi, Peng-Fei Jia, Yuan Bao, Hong-Ju Li, Wei-Cai Yang

2022, 49(1): 30-39. doi: 10.1016/j.jgg.2021.10.002

Abstract (461) PDF (64)

Abstract:
Nucleolus is a membrane-less organelle where ribosomes are assembled, and ribosomal RNAs (rRNAs) transcribed and processed. The assembled ribosomes composed of ribosomal proteins and rRNAs synthesize proteins for cell survival. In plants, the loss of nucleolar ribosomal proteins often causes gametophytically or embryonically lethality. The amount of rRNAs are under stringent regulation according to demand and partially switched off by epigenetic modifications. However, the molecular mechanism for the selective activation or silencing is still unclear, and the transcriptional coordination of rRNAs and ribosomal proteins is also unknown. Here, we report the critical role of three Arabidopsis nucleolar proteins HDT1, HDT2, and HDT3 in fertility and transcription of rDNAs and rRNA processing-related genes through histone acetylation. This study highlights the important roles of transcriptional repression of ribosome biogenesis-related genes for plant reproductive development.

FGF8-mediated signaling regulates tooth developmental pace during odontogenesis

Chensheng Lin, Ningsheng Ruan, Linjun Li, Yibin Chen, Xiaoxiao Hu, YiPing Chen, Xuefeng Hu, Yanding Zhang

2022, 49(1): 40-53. doi: 10.1016/j.jgg.2021.08.009

Abstract (298) PDF (24)

Abstract:
The developing human and mouse teeth constitute an ideal model system to study the regulatory mechanism underlying organ growth control since their teeth share highly conserved and well-characterized developmental processes, and their developmental tempo varies notably. In the current study, we manipulated heterogenous recombination between human and mouse dental tissues and demonstrated that the dental mesenchyme dominates the tooth developmental tempo and FGF8 could be a critical player during this developmental process. Forced activation of FGF8 signaling in the dental mesenchyme of mice promoted cell proliferation, prevented cell apoptosis via p38 and perhaps PI3K-Akt intracellular signaling, and impelled the transition of the cell cycle from G1- to S-phase in the tooth germ, resulting in the slowdown of the tooth developmental pace. Our results provide compelling evidence that extrinsic signals can profoundly affect tooth developmental tempo, and the dental mesenchymal FGF8 could be a pivotal factor in controlling the developmental pace in a non-cell-autonomous manner during mammalian odontogenesis.

Identification of novel loci influencing refractive error in East Asian populations using an extreme phenotype design

Xiaotong Han, Tianzi Liu, Xiaohu Ding, Jialin Liu, Xingyan Lin, Decai Wang, Moeen Riaz, Paul N. Baird, Zhi Xie, Yuan Cheng, Yi Li, Yuki Mori, Masahiro Miyake, Hengtong Li, Ching-Yu Cheng, Changqing Zeng, Kyoko Ohno-Matsui, Xiangtian Zhou, Fan Liu, Mingguang He

2022, 49(1): 54-62. doi: 10.1016/j.jgg.2021.08.011

Abstract (241) PDF (13)

Abstract:
The global "myopia boom" has raised significant international concerns. Despite a higher myopia prevalence in Asia, previous large-scale genome-wide association studies (GWASs) were mostly based on European descendants. Here, we report a GWAS of spherical equivalent (SE) in 1852 Chinese Han individuals with extreme SE from Guangzhou (631 < -6.00D and 574 > 0.00D) and Wenzhou (593 < -6.00D and 54 > -1.75D), followed by a replication study in two independent cohorts with totaling 3538 East Asian individuals. The discovery GWAS and meta-analysis identify three novel loci, which show genome-wide significant associations with SE, including 1q25.2 FAM163A, 10p11.22 NRP1/PRAD3, and 10p11.21 ANKRD30A/MTRNR2L7, together explaining 3.34% of SE variance. 10p11.21 is successfully replicated. The allele frequencies of all three loci show significant differences between major continental groups (P<0.001). The SE reducing (more myopic) allele of rs10913877 (1q25.2 FAM163A) demonstrates the highest frequency in East Asians and much lower frequencies in Europeans and Africans (EAS = 0.60, EUR = 0.20, and AFR = 0.18). The gene-based analysis additionally identifies three novel genes associated with SE, including EI24, LHX5, and ARPP19. These results provide new insights into myopia pathogenesis and indicate the role of genetic heterogeneity in myopia epidemiology among different ethnicities.

Essential role of Msx1 in regulating anterior-posterior patterning of the secondary palate in mice

Shicheng Zhu, Hanjing Song, Liangjun Zhong, Suman Huo, Yukun Fang, Wanxin Zhao, Xueqin Yang, Zhong-Min Dai, Rui He, Mengsheng Qiu, Zunyi Zhang, Xiao-Jing Zhu

2022, 49(1): 63-73. doi: 10.1016/j.jgg.2021.07.006

Abstract (171) PDF (10)

Abstract:
Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis; however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1 in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1 (RosaMsx1) throughout the palatal mesenchyme leads to cleft palate in mice, associated with aberrant cell proliferation and cell death. Osteogenic patterning of the hard palate in RosaMsx1 mice is severely impaired, as revealed by a marked reduction in palatine bone formation and decreased expression of the osteogenic regulator Sp7. Overexpression and knockout of Msx1 in mice show that the transcription repressor promotes the expression of the anterior palate-specific Alx1 but represses the expression of the medial-posterior palate genes Barx1, Meox2, and Tbx22. Furthermore, Tbx22 constitutes a direct Msx1 target gene in the secondary palate, suggesting that Msx1 can directly repress the expression of medial-posterior specific genes. Finally, we determine that Sp7 is downstream of Tbx22 in palatal mesenchymal cells, suggesting that a Msx1/Tbx22/Sp7 axis participates in the regulation of palate development. Our findings unveil a novel role for Msx1 in regulating the anterior-posterior growth and patterning of the secondary palate.

Genetic and epigenetic control on clock genes in multiple sclerosis

Tarek K. Motawi, Olfat G. Shaker, Soha O. Hassanin, Shaymaa G. Ibrahim, Mahmoud A. Senousy

2022, 49(1): 74-76. doi: 10.1016/j.jgg.2021.07.016

Abstract (194) PDF (24)

Abstract:

Whole-genome sequences shed light on the demographic history and contemporary genetic erosion of free-ranging jaguar (Panthera onca) populations

Gustavo P. Lorenzana, Henrique V. Figueiró, Christopher B. Kaelin, Gregory S. Barsh, Jeremy Johnson, Elinor Karlsson, Ronaldo G. Morato, Dênis A. Sana, Laury Cullen, Joares A. May, Edsel A. Moraes, Daniel L.Z. Kantek, Leandro Silveira, William J. Murphy, Oliver A. Ryder, Eduardo Eizirik

2022, 49(1): 77-80. doi: 10.1016/j.jgg.2021.10.006

Abstract (320) PDF (39)

Abstract:

Kilobase-scale genomic deletion of DOTFL1 in Dendrobium orchids

Yan Li, Bin Zhang, Hao Yu

2022, 49(1): 81-84. doi: 10.1016/j.jgg.2021.07.008

Abstract (195) PDF (17)

Abstract:

Zfp281 is essential for epiblast maturation through a cell autonomous effect

Ruge Zang, Xin Huang, Dan Li, Hongwei Zhou, Shaorong Gao, Jianlong Wang

2022, 49(1): 85-88. doi: 10.1016/j.jgg.2021.08.016

Abstract (281) PDF (31)

Abstract:

2022 Vol. 49, No. 1