The study of homeotic-transformation mutants in model organisms such as Drosophila revolutionized the field of developmental biology, but how these mutants relate to human developmental defects remains to be elucidated. Here, we show that Liebenberg syndrome, an autosomal-dominant upper-limb malformation, shows features of a homeotic limb transformation in which the arms have acquired morphological characteristics of a leg. Using high-resolution array comparative genomic hybridization and paired-end whole-genome sequencing, we identified two deletions and a translocation 5' of PITX1. The structural changes are likely to remove active PITX1 forelimb suppressor and/or insulator elements and thereby move active enhancer elements in the vicinity of the PITX1 regulatory landscape. We generated transgenic mice in which PITX1 was misexpressed under the control of a nearby enhancer and were able to recapitulate the Liebenberg phenotype.
Early childhood caries (ECC) is the most common noncommunicable childhood disease-an important health problem with known environmental and social/behavioral influences lacking consensus genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multiancestry population of U.S.
Deficient Anterior pituitary with common Variable Immune Deficiency (DAVID) syndrome is caused by heterozygous mutations leading to adrenocorticotropic hormone deficiency and immune system issues.
Researchers created pituitary organoids from edited human stem cells to study how specific genetic mutations affect pituitary development and found that these mutations significantly reduced the number of hormone-producing cells called corticotrophs.
The study identified changes in gene expression related to pituitary development and suggested that the observed mutations have a direct impact on endocrine function, classifying them as pathogenic for pituitary development.
Breast cancer is the most prevalent cancer in women, affecting over 2 million annually and leading to 650,000 deaths, but its epigenetic factors are still not fully understood.
The study used data from The Cancer Genome Atlas and various omics datasets to identify significant features related to breast cancer, narrowing down from 417,486 to 2,701 relevant markers using advanced analytics methods.
Findings revealed that cancer samples exhibited lower gene expression and higher methylation values, with potential regulatory mechanisms involving transcription factors and 3D chromatin structure, indicating fruitful avenues for new biomarkers and treatments.
Cutaneous wounds heal slowly and often result in scarring, whereas oral wounds heal more rapidly due to differences in cellular responses in the skin and oral epithelium.
The transcription factor PITX1 is abundant in oral epithelial cells but absent in skin cells, and researchers wanted to see if introducing PITX1 into skin cells could improve healing.
By inserting PITX1 in mouse skin, they found it enhanced keratinocyte migration and proliferation, changed cell communication to resemble oral tissue, and resulted in faster healing compared to normal skin.
We conducted the first genome-wide association study (GWAS) of colorectal cancer (CRC) in Taiwan with 5342 cases and 61,015 controls. Ninety-two SNPs in three genomic regions reached genome-wide significance (p < 5 × 10). The lead SNPs in these three regions were: rs12778523 (OR = 1.
