Kwondo Kim

The genome landscape of indigenous African cattle

BackgroundThe history of African indigenous cattle and their adaptation to environmental and human selection pressure is at the root of their remarkable diversity. Characterization of this diversity is an essential step towards understanding the genomic basis of productivity and adaptation to survival under African farming systems.ResultsWe analyze patterns of African cattle genetic variation by sequencing 48 genomes from five indigenous populations and comparing them to the genomes of 53 commercial taurine breeds. We find the highest genetic diversity among African zebu and sanga cattle. Our search for genomic regions under selection reveals signatures of selection for environmental adaptive traits. In particular, we identify signatures of selection including genes and/or pathways controlling anemia and feeding behavior in the trypanotolerant N’Dama, coat color and horn development in Ankole, and heat tolerance and tick resistance across African cattle especially in zebu breeds.ConclusionsOur findings unravel at the genome-wide level, the unique adaptive diversity of African cattle while emphasizing the opportunities for sustainable improvement of livestock productivity on the continent.

ATRX induction by mutant huntingtin via Cdx2 modulates heterochromatin condensation and pathology in Huntington's disease

Aberrant chromatin remodeling is involved in the pathogenesis of Huntingtons disease (HD) but the mechanism is not known. Herein, we report that mutant huntingtin (mtHtt) induces the transcription of alpha thalassemia/mental retardation X linked (ATRX), an ATPase/helicase and SWI/SNF-like chromatin remodeling protein via Cdx-2 activation. ATRX expression was elevated in both a cell line model and transgenic model of HD, and Cdx-2 occupancy of the ATRX promoter was increased in HD. Induction of ATRX expanded the size of promyelocytic leukemia nuclear body (PML-NB) and increased trimethylation of H3K9 (H3K9me3) and condensation of pericentromeric heterochromatin, while knockdown of ATRX decreased PML-NB and H3K9me3 levels. Knockdown of ATRX/dXNP improved the hatch rate of fly embryos expressing mtHtt (Q127). ATRX/dXNP overexpression exacerbated eye degeneration of eye-specific mtHtt (Q127) expressing flies. Our findings suggest that transcriptional alteration of ATRX by mtHtt is involved in pericentromeric heterochromatin condensation and contributes to the pathogenesis of HD.

A multifunctional protein EWS regulates the expression of Drosha and microRNAs

EWS (Ewing’s Sarcoma) gene encodes an RNA/DNA-binding protein that is ubiquitously expressed and involved in various cellular processes. EWS deficiency leads to impaired development and early senescence through unknown mechanisms. We found that EWS regulates the expression of Drosha and microRNAs (miRNAs). EWS deficiency resulted in increased expression of Drosha, a well-known microprocessor, and increased levels of miR-29b and miR-18b. Importantly, miR-29b and miR-18b were directly involved in the post-transcriptional regulation of collagen IV alpha 1 (Col4a1) and connective tissue growth factor (CTGF) in EWS knock-out (KO) mouse embryonic fibroblast cells. The upregulation of Drosha, miR-29b and miR-18b and the sequential downregulation of Col4a1 and CTGF contributed to the deregulation of dermal development in EWS KO mice. Otherwise, knockdown of Drosha rescued miRNA-dependent downregulation of Col4a1 and CTGF proteins. Taken together, our data indicate that EWS is involved in post-transcriptional regulation of Col4a1 and CTGF via a Drosha–miRNA-dependent pathway. This finding suggests that EWS has a novel role in dermal morphogenesis through the modulation of miRNA biogenesis.

Genome sequence of pacific abalone (Haliotis discus hannai): the first draft genome in family Haliotidae

Abstract Background: Abalones are large marine snails in the family Haliotidae and the genus Haliotis belonging to the class Gastropoda of the phylum Mollusca. The family Haliotidae contains only one genus, Haliotis, and this single genus is known to contain several species of abalone. With 18 additional subspecies, the most comprehensive treatment of Haliotidae considers 56 species valid [1]. Abalone is an economically important fishery and aquaculture animal that is considered a highly prized seafood delicacy. The total global supply of abalone has increased 5-fold since the 1970s and farm production increased explosively from 50 mt to 103 464 mt in the past 40 years. Additionally, researchers have recently focused on abalone given their reported tumor suppression effect. However, despite the valuable features of this marine animal, no genomic information is available for the Haliotidae family and related research is still limited. To construct the H. discus hannai genome, a total of 580-G base pairs using Illumina and Pacbio platforms were generated with 322-fold coverage based on the 1.8-Gb estimated genome size of H. discus hannai using flow cytometry. The final genome assembly consisted of 1.86 Gb with 35 450 scaffolds (>2 kb). GC content level was 40.51%, and the N50 length of assembled scaffolds was 211 kb. We identified 29 449 genes using Evidence Modeler based on the gene information from ab initio prediction, protein homology with known genes, and transcriptome evidence of RNA-seq. Here we present the first Haliotidae genome, H. discus hannai, with sequencing data, assembly, and gene annotation information. This will be helpful for resolving the lack of genomic information in the Haliotidae family as well as providing more opportunities for understanding gastropod evolution.

RNA-seq analysis for detecting quantitative trait-associated genes.

Many recent RNA-seq studies were focused mainly on detecting the differentially expressed genes (DEGs) between two or more conditions. In contrast, only a few attempts have been made to detect genes associated with quantitative traits, such as obesity index and milk yield, on RNA-seq experiment with large number of biological replicates. This study illustrates the linear model application on trait associated genes (TAGs) detection in two real RNA-seq datasets: 89 replicated human obesity related data and 21 replicated Holsteins’ milk production related RNA-seq data. Based on these two datasets, the performance between suggesting methods, such as ordinary regression and robust regression, and existing methods: DESeq2 and Voom, were compared. The results indicate that suggesting methods have much lower false discoveries compared to the precedent two group comparisons based approaches in our simulation study and qRT-PCR experiment. In particular, the robust regression outperforms existing DEG finding method as well as ordinary regression in terms of precision. Given the current trend in RNA-seq pricing, we expect our methods to be successfully applied in various RNA-seq studies with numerous biological replicates that handle continuous response traits.

Characterizing Milk Production Related Genes in Holstein Using RNA-seq

Although the chemical, physical, and nutritional properties of bovine milk have been extensively studied, only a few studies have attempted to characterize milk-synthesizing genes using RNA-seq data. RNA-seq data was collected from 21 Holstein samples, along with group information about milk production ability; milk yield; and protein, fat, and solid contents. Meta-analysis was employed in order to generally characterize genes related to milk production. In addition, we attempted to investigate the relationship between milk related traits, parity, and lactation period. We observed that milk fat is highly correlated with lactation period; this result indicates that this effect should be considered in the model in order to accurately detect milk production related genes. By employing our developed model, 271 genes were significantly (false discovery rate [FDR] adjusted p-value<0.1) detected as milk production related differentially expressed genes. Of these genes, five (albumin, nitric oxide synthase 3, RNA-binding region (RNP1, RRM) containing 3, secreted and transmembrane 1, and serine palmitoyltransferase, small subunit B) were technically validated using quantitative real-time polymerase chain reaction (qRT-PCR) in order to check the accuracy of RNA-seq analysis. Finally, 83 gene ontology biological processes including several blood vessel and mammary gland development related terms, were significantly detected using DAVID gene-set enrichment analysis. From these results, we observed that detected milk production related genes are highly enriched in the circulation system process and mammary gland related biological functions. In addition, we observed that detected genes including caveolin 1, mammary serum amyloid A3.2, lingual antimicrobial peptide, cathelicidin 4 (CATHL4), cathelicidin 6 (CATHL6) have been reported in other species as milk production related gene. For this reason, we concluded that our detected 271 genes would be strong candidates for determining milk production.

Cattle genome-wide analysis reveals genetic signatures in trypanotolerant N'Dama

BackgroundIndigenous cattle in Africa have adapted to various local environments to acquire superior phenotypes that enhance their survival under harsh conditions. While many studies investigated the adaptation of overall African cattle, genetic characteristics of each breed have been poorly studied.ResultsWe performed the comparative genome-wide analysis to assess evidence for subspeciation within species at the genetic level in trypanotolerant N’Dama cattle. We analysed genetic variation patterns in N’Dama from the genomes of 101 cattle breeds including 48 samples of five indigenous African cattle breeds and 53 samples of various commercial breeds. Analysis of SNP variances between cattle breeds using wMI, XP-CLR, and XP-EHH detected genes containing N’Dama-specific genetic variants and their potential associations. Functional annotation analysis revealed that these genes are associated with ossification, neurological and immune system. Particularly, the genes involved in bone formation indicate that local adaptation of N’Dama may engage in skeletal growth as well as immune systems.ConclusionsOur results imply that N’Dama might have acquired distinct genotypes associated with growth and regulation of regional diseases including trypanosomiasis. Moreover, this study offers significant insights into identifying genetic signatures for natural and artificial selection of diverse African cattle breeds.

Application of LogitBoost Classifier for Traceability Using SNP Chip Data

Consumer attention to food safety has increased rapidly due to animal-related diseases; therefore, it is important to identify their places of origin (POO) for safety purposes. However, only a few studies have addressed this issue and focused on machine learning-based approaches. In the present study, classification analyses were performed using a customized SNP chip for POO prediction. To accomplish this, 4,122 pigs originating from 104 farms were genotyped using the SNP chip. Several factors were considered to establish the best prediction model based on these data. We also assessed the applicability of the suggested model using a kinship coefficient-filtering approach. Our results showed that the LogitBoost-based prediction model outperformed other classifiers in terms of classification performance under most conditions. Specifically, a greater level of accuracy was observed when a higher kinship-based cutoff was employed. These results demonstrated the applicability of a machine learning-based approach using SNP chip data for practical traceability.

The Genetic Origin of Short Tail in Endangered Korean Dog, DongGyeongi

The tail of many animal species is responsible for various physiological functions. The functional importance of tail may have brought tail-loss to attention in many evolutionary and developmental studies. To provide a better explanation for the loss of tail, the current study aims to identify the evolutionary history and putative causal variants for the short tail in DongGyeongi (DG), an endangered dog breed, which is also the only dog in Korea that possesses a short tail. Whole genome sequencing was conducted on 22 samples of DG, followed by an investigation of population stratification with 10 other dog breeds. The genotypes, selective sweep and demography of DG were also investigated. As a result, we discovered the unique genetic structure of DG and suggested two possible ways in which the short tail phenotype developed. Moreover, this study suggested that selective sweep genes, ANKRD11 and ACVR2B may contribute to the reduction in tail length, and non-synonymous variant in the coding sequence of T gene and the CpG island variant of SFRP2 gene are the candidate causal variants for the tail-loss.

Whole genome sequencing of Gyeongbuk Araucana, a newly developed blue-egg laying chicken breed, reveals its origin and genetic characteristics.

Chicken, Gallus gallus, is a valuable species both as a food source and as a model organism for scientific research. Here, we sequenced the genome of Gyeongbuk Araucana, a rare chicken breed with unique phenotypic characteristics including flight ability, large body size, and laying blue-shelled eggs, to identify its genomic features. We generated genomes of Gyeongbuk Araucana, Leghorn, and Korean Native Chicken at a total of 33.5, 35.82, and 33.23 coverage depth, respectively. Along with the genomes of 12 Chinese breeds, we identified genomic variants of 16.3 million SNVs and 2.3 million InDels in mapped regions. Additionally, through assembly of unmapped reads and selective sweep, we identified candidate genes that fall into heart, vasculature and muscle development and body growth categories, which provided insight into Gyeongbuk Araucana’s phenotypic traits. Finally, genetic variation based on the transposable element insertion pattern was investigated to elucidate the features of transposable elements related to blue egg shell formation. This study presents results of the first genomic study on the Gyeongbuk Araucana breed; it has potential to serve as an invaluable resource for future research on the genomic characteristics of this chicken breed as well as others.