Genomic Structural Variants

In recent years, genome-wide association studies (GWAS) have successfully tagged thousands of disease- or trait-associated genetic loci. However, molecular mechanisms linking the locus to the disease phenotype often remain unclear. Moreover, for most complex diseases and traits, associations found in GWAS explain only a small proportion of the phenotypic variation (129, 130). For example, although 71 independent loci have been associated with Crohn 's Disease, they account for only 23% of the estimated heritability (131). GWAS of psychiatric diseases show an even less favorable picture. For instance, schizophrenia has an estimated heritability of 80% (132, 133), but observed genetic variants currently account for less than 1% of the variance (134). To bridge this gap between genotype and disease phenotype and to better understand the biological mechanisms and translational possibilities, the genotype-driven approach, aided with deep phenotyping, appears to be a more appealing and powerful strategy (135, 136). A limitation of this approach however, is that the disease pathologies are often tissue- or cell type-specific (137-141), and due to ethical and practical reasons, deep phenotyping analyses are often only feasible in easily available surrogate tissues such as blood, particularly in large population-based gene identification studies. The iPSC technologies discussed here in this chapter, along with new sequencing technologies, genome-wide assays, and comprehensive genome

The Human Genome Project is a worldwide research effort with the goal of analyzing the structure of human DNA and determining the location of the estimated 100,000 human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the

Over the last 10 years scientists have been involved in the progression and completion of the Human Genome Project. "Scientists working on this project have developed detailed maps that identify the

Imagine if one day, humans were modified to be better people. Well that day is almost here, because scientists have already attempted to genetically modifying humans in China (OI). Although humans have the chance to be modified to be better, is that really a good thing? Genetically modifying humans is not a good idea. For example one of the modifications is to help people not feel pain, but it can also keep them unaware of harm (Doc. 2). Furthermore genetic modifications on humans is not good and shouldn't be allowed.

Braun tells me that there are possibly a million SNPs in each person, though only a small fraction are tightly linked with common ailments. These disease-causing SNPs are fueling a biotech bonanza; the hope is that after finding them, the discoverers can design wonder drugs. In the crowded SNP field, Sequenom vies with Iceland-based deCode Genetics, American companies such as Millennium Pharmaceuticals, Orchid

CHARGE syndrome is a genetic condition believed to be the result of a sporadic heterozygous mutation in the CHD7 gene. Experiments to determine the precise mutations within the CHD7 gene have concluded that mutations are scattered throughout the gene and include nonsense, frameshift and missense mutations as well as intragenic deletions (Martínez-Quintana et al., 2014). Intragenic deletions were initially reported in 2004 by a team who optimized array comparative genome hybridization (CGH) for high-resolution genome-wide screening of copy-number variations. Array CGH has since become a valuable, genome-wide screening tool for the detection of chromosomal aberrations in the form of copy number imbalances. By utilizing array CGH in two individuals with CHARGE syndrome, the team was able to report a 2.3 Mb de novo overlapping microdeletion on chromosome 8q12 (Vissers et al., 2004).

The book begins by exploring gene variations in the human genome, and finding genes that show “strong signs of selection” over the last 10,000 years or so. This is possible due to relatively recent

Though HAR1 was present in other species, it had evolved extremely slowly until the emergence of humans. “The fact that HAR1 was essentially frozen in time through hundreds of millions of years indicates that it does something very important; that it then underwent abrupt revision in humans suggests that this function was significantly modified in our lineage,” writes Pollard. HAR1 is named so because it seems to have rapidly evolved after humans and chimpanzees split from a common ancestor. HAR1 is also unique in that it does not encode a protein. Before the research done and discoveries made by the Human Genome Project, scientists previously thought that all genes required proteins as the building blocks to their sequencing. Researchers now know that these protein-encoded genes make up only 1.5 percent of our DNA. The other 98.5 percent – sometimes referred to as junk DNA – contains regulatory sequences that tell other genes when to turn on and off. “…You do not need to change very much of the genome to make a new species. The way to evolve a human from a chimp-human ancestor is not to speed the ticking of the molecular clock as a

The Human Genome Project, also known as HGP has helped our society crack the code in the small differences between human DNA that make up our health and can already pinpoint future illnesses. HPG was an international joint research preparation with the goal of mapping and trying to understand all the human genes sequences through generations. Researchers have been able to decode our genomes and understand them in three different ways. First off they have been able to see that our genome’s DNA has a certain order, and that order helps make up who we are; Secondly they are able to map where certain genes are and where they are located on the chromosomes. And third, being able to produce “linkage maps” that can help track inherited traits

In February 2001, Venter et al., reported on the “penultimate milestone” – the feat of mapping 95% of the euchromatic portion of the human genome (Venter et al., 2001). Multiple discoveries were made in the process of mapping the human genome: the number of genes (fewer than imagined); the percent difference between individuals (less than 0.1%); and new techniques (Polymerase Chain Reaction) (Venter et al., 2001; National Human Genome Research Institute, 2012).

2. The authors studied this subject as it relates to a very prevalent medical diagnosis around the world, Adolescent idiopathic Scoliosis (AIS). This medical illness is the most common spinal deformity found in children from the age of 10 to the end of the pubertal growth spurt and can be very debilitating.1 The authors decided to study single nucleotide polymorphisms (SNP) and there effects on gene expression and protein regulation that may be linked to the disease because they had previously done a genome wide-association study where they identified two loci that were linked to AIS in a Japanese female population.1 This study was also replicated in Chinese and Caucasian ppulations.1 They knew they were on the right track that SNP’s and specific locations on the chromosome were linked to the disease and that they should look further into it. However, this link only explained an approximate 1% genetic variance in AIS and therefore the authors decided they should identify more susceptibility to genes and use a larger gene pool in their study. 1 They also conducted a whole genome imputation. 1

Jorde, L. B., Bamshad, M. J., White, R. L. and John C. Carey MD MPH Dr. (2006) Medical genetics updated edition for 2006 – 2007. 3rd edn. United States: Mosby.

The Human Genome Project (HGP), an international scientific research project, has educated the public tremendously on various topics concerning DNA and genetics. This study has been beneficial to communities alike. As stated, the HGP sought to identify all the genes in human DNA, determine the sequences of the three billion chemical base pairs that make up human DNA, store this information in databases, improve tools for data analysis, transfer related technologies to the private sector, and address the ethical, legal, and social issues that may arise from the project. In favor of achieving these goals, scientists studied the genetic makeup of several nonhuman organisms (Human Genome Management Information System, 2011).

DeSalle and Michael Yudell. Welcome To The Genome: A User’s Guide to Genetic Past, Present, and Future. Canada: John Wiley & Sons. Inc., 2005. Print.

Genetic mutations are important for tracking disease abnormalities and if there are any causal links between unsuspecting genes and diseases. Not