Genomic approaches to studying human-specific developmental traits

Abstract

Changes in developmental regulatory programs drive both disease and phenotypic differences among species. Linking human-specific traits to alterations in development is challenging, because we have lacked the tools to assay and manipulate regulatory networks in human and primate embryonic cells. This field was transformed by the sequencing of hundreds of genomes -human and non-humanthat can be compared to discover the regulatory machinery of genes involved in human development. This approach has identified thousands of human-specific genome alterations in developmental genes and their regulatory regions. With recent advances in stem cell techniques, genome engineering, and genomics, we can now test these sequences for effects on developmental gene regulation and downstream phenotypes in human cells and tissues.

Language Impairments in ASD Resulting from a Failed Domestication of the Human Brain

“…Some comprehensive accounts of the human condition set against the cognitive profiles of other primates have been recently put forth (Seed and Tomasello, 2010; Platt et al, 2016). Comparative genomics also provides valuable information about the sources of the observed differences and similarities in the human genome (Rogers and Gibbs, 2014; Franchini and Pollard, 2015). Likewise, we are beginning to achieve an advanced understanding of the genetic changes that occurred after our split from extinct hominins (Pääbo, 2014; Zhou et al, 2015).…”

Stem Cells: A Renaissance in Human Biology Research

“…Alternatively, human DNA can be directly inserted into animal genomes such as the mouse or zebrafish and create transgenic animals for interrogation of human-specific traits in vivo. Transgenic animal models have been instructive for understanding the functions of several coding and non-coding human DNA sequences (reviewed by Franchini and Pollard [2015]). Another application of the transgenic approach is to generate improved ''humanized'' mouse models by introducing human specific factors, such as human leukocyte antigen (HLA) molecules and cytokines, into immunodeficient mice for better and broader engraftment of multiple types of human cells and tissues (Brehm et al, 2014).…”

Not All Stem Cells Are Equally Great: Donor Single-Nucleotide Polymorphisms (SNP) May Matter More Than Previously Thought

“…We can now anticipate that as our understanding of genetic etiology of these diseases grows, future studies will further explore common or rare genetic variations contributing to diseases as well as many physiological and pathophysiological processes such as aging, tissue homeostasis and regeneration. 16,17 Genetic studies are rapidly expanding into stem cell research and regenerative medicine models and the study of stem cell genomics has been emerging to have wide implications in biology and possible therapeutic applications of stem cells. 18,19 Genetic traits at the DNA level are reflected in stem cells originated from a donor although transcriptome and epigenome may understandable vary in different tissue and cell types.…”