GENETICS and GENOMIC

What is genetics?

«Genetics is the branch of science concerned with genes, heredity, and variation in living organisms. It seeks to understand the process of trait inheritance from parents to offspring, including the molecular structure and function of genes, gene behavior in the context of a cell or organism (e.g. dominance and epigenetics), gene distribution, and variation and change in populations.» Nature.

History of Genetics

1866; Gregor Mendel published his theory of inheritance.

1871; Friedrich Miescher published his discovery of nuclein.

1900; Mendel’s work is acknowledged by European botanists.

1902; Walter Sutton and Theodor Boveri proposed chromosome theory of inheritance.

1905; The term ‘genetics’ was used for the first time by William Bateson.

1908; Hardy-Weinberg equilibrium has been introduced; the frequency of allelesand genotypes remains constant unless influences occur like non-random mating, mutation, selection etc.

1910; Thomas Hunt Morgan linked fruit flies X-chromosome with white eyes

1927; Herman Muller studied on radiation effects on mutation

1944; Oswald Avery discovered that transforming principle is DNA. 1951; Frederick Sanger sequenced the insulin protein chain. 1952; Rosalind Franklin produced ‘Photo 51’ of DNA. 1953; James Watson and Francis Crick published theDouble-helix structure of DNA 1956; Joe Hin Tijo discovered correct chromosome number of humans by using colchicine1961; Francis Crick and Sydney Brenner deciphered geneticcode; three bases code for one amino acid. 1961; Jacques Monod, François Jacob and Arthur Pardee has revealed the mechanism of gene expression regulation. 1970; Hamilton Smith discovered the first restriction enzymes. 1975; Geneticists agreed guidelines on recombinant research. 1996; Ian Wilmut, Keith Campbell and colleagues has succesfullycloned a mammal ‘Dolly’ from somatic cell.

Areas of Genetics;

Classical genetics

Molecular genetics

Behavioral genetics

Clinical genetics

Population, quantitative and ecological genetics

Genomics

Classical Genetics;

• Consist of the techniques and methodologies of genetics that predate the advent of molecular biology.

• Basis for all other fields of genetics.

• Primarily concerned by how genetic traits transmitted.

Moleuclar genetics

• Focuses on the structure and function of genes at molecular level.

• Uses both molecular biology and classical genetictechniques.

Behavorial genetics;

• Study role of genetics in animal behaviour.

• Highly interdicciplinary, involves contributions fromvarious fields.

• In humans usually twin studies or adoption studies areused.

Medical genetics

• Study diagnoses of disorders and birth defects causedby genetic mechanisms.

Population, quantitative and ecological genetics;

• Population genetics study the distribution of and change in allele frequencies of genes under the influence of the four evolutionary forces: natural selection, genetic drift, mutation and migration.

• Quantitative genetics focus on continously varying phenptypes.

• Ecological genetics focuses on wild populations of organisms andcollects data from ecological aspects and molecular markers fromindividuals and explain the relation between them.

Genomics;

Genome is an organism’s complete set of genetic material withcodin and noncoding sites. For humans it is DNA, for RNA viruses it is RNA.

Mitochonria and chloroplas have their own DNA.

Human genome has 23 chromosomes, 20,000-25,000 genes.

Genomics is sequencing and analyzing an organismsgenome and gene interactions.

How does genetic and genomic differ?

Genetic focuses on functioning and composition of single gene, on the other hand genomic studies on all genes and their inter relationships to understand their cooperation on growth and development of organisms and diseases.

Goals of genomics

Collect the data of organism’s genome sequences.

Search out the location of the genes for analyzing spatialrelationships and annotate the gene set in a genome

Learn the function of genes.

Establish how gene expression profiles vary under differentdifferent conditions.

Compare gene and protein profiles among different organisms tolearn about evalutionary relationships.

History of genomics;

1977; Frederick Sanger sequenced first DNA genome.

1983; Huntington disease gene was mapped.

1988; The Human Genome Organization (HUGO) was founded.

1990; The Human Genome Project has been launched.

1996; First complete genome of a eukaryotic organism

Saccharomyces cerevisiae was sequenced.

1999; First human chromosome, chromosome 22, has been sequenced.

2002; HapMap project was released.

2003; Human genome sequence completed and published at the 50th anniversary of DNA double helix discovery. 2005; Cancer Genome Atlas and Cancer Genome Project were launched. 2005; Welcome Trust has established Case Control Consortium. 2006; Global differences in copy number variation has been reported. 2007; First results from Case Control Consrotium was launched. 2008; International Cancer Genome Consortium has been launched. 2009; First complete cancer genomes has been sequenced2010; Human Heredity and Health (H3 Africa) has been launched. 2010; UK10K has been launched to discover more rare variants. 2010; Draft of Neanderthal genome sequence has been published.2012; Denisovan genome has been sequenced.

http://wellcomelibrary.org/collections/digital-collections/makers-of-modern-genetics/genetics-timeline/#28106

Target selecton

• Genomic DNA, RNA, Mitochondrial DNA, Chloroplast DNA

Sequencing

• Basic methods, like Sanger

• Advanced methods and de novo sequencing, like shotgun sequencing

• Next generation methods, like Illumina, Ion Torrent

Assembly

• De novo assembly, for genomes that doesn’t have any reference

• Comparative assembly, base on closely related organism’s genome sequence

Annotation

• Identifying portions of the genome that do not code for proteins

• Gene prediction; identification of elements on the genome

• Attaching biological information to these elements

Genome Analysis

Subfields of genomics;

Structural genomics

Functional genomics

Comparative genomics

Comparative genomics;

• Aims to compare genomic features between different species forbetter understanding the evaloutionary relationships.

• Principle of comparative genomics base on that common featuresof two different organism will often be encoded by evolutionarlyconserved genes.

• Comparative genomics focuses on both similarities and differencesof proteins, RNA and regulatory regions of different organisms.

Structural genomics;

• Aims to determine structure of every protein encoded by thegenome.

• Identify novel protein folds and 3-D structures for betterunderstanding the functions of proteins.

Functional genomics;

• Aims to collect and use data from sequencing for decribing gene and protein functions and interactions for revealing therelationship between an organisms genome and phenotype.

• Focuses on dynamic aspects like, transcription, translation andprotein-protein interactions.

• Promises better understanding of an organisms dynamic propertiesby synthesizing genomic and proteomic knowledge.

Related fields of genomics

Systems Biology• Computational and mathematical modeling of complex biological

systems.

• Study the interactions between biological systems and theircomponents and how these interactions affect the system.

Pharmacogenomics• Study how variatons of individuals genome sequences may effect the

drug respoenses.

• Aims to develop more personal therapies to patients and seperate theresponding and non-responding patients.

Chemogenomics• Systematic screening of targeted librarires of small molecules

against individual drug target families.

• Use active compounds that action as ligands to characterizeproteome functions to integrate target and drug discovery.

Proteomics• Proteome is entire set of proteins produced by an organism.

• Proteomics is large scale study of proteome, for understandingprotein interactions, functions and structures.

Glycomics• Glycome is an organism’s entire complement of free or complex

sugars. • Glycomics is study of glycomes for undertsanding how a collection of

glycans relates to a particular biological event.

Metabolomics• Metabolome is collection of all metabolites (intermediates and

products of metabolism) in an organism’s cell, tissue or organ. • Metabolomics compare the relative difference between

biological samples based on metabolite profiles.

Human genome project

Coordinated by,

Department of Energy and

National Institute of Health

Goals;

Identify the approximate genes in human DNA

Determine the sequence of human genome

Create a human genome database

Develop data analysis tools.

Transfer related technologies to the private sector.

ED Green et al. Nature 470, 204-213 (2011) doi:10.1038/nature09764

What is next?

Goals;

• Define patterns of genetic variation across human genome

• Guide selection of SNPs efficiently to “tag” common variants

• Public release of all data (assays, genotypes)

Tool for finding genes and genetic variations that affect health anddisease.

Resource for studying the genetic factors contributing to variation in response to environmental factors.

Founded by,• National Cancer Institute and

• National Human Genome Research Institute

They are studying on more than 20 different types of human cancer. They compare camcer and normal tissue taken from same patient.

Goals;

• Revealing the mutations on cell cycle control mechanisms.

• Determining signatures for cancer types to lead doctors for better diagnosis and treatment.

Funded by Welcome Trust

Goals; Compare common variants in the genomes of patients, who have common diseases like diabetes, high blood pressure, bipolar diease, etc.

Goals; • Coordinate the generation of comprehensive catalogues of genomic

abnormalities (somatic mutations) in tumors in 50 different cancer types and/or subtypes which are of clinical and societal importance across the globe.

• Generate complementary catalogues of transcriptomic and epigenomicdatasets from the same tumors.

• Make the data available to the entire research community as rapidly as possible, and with minimal restrictions, to accelerate research into the causes and control of cancer

Funded by, • The US National Instıtutes of Health and

• The Welcome Trust.

Goals; • Create and support a pan-continental network of laboratories that

will be equipped to apply leading-edge research to the study of the complex interplay between environmental and genetic factors which determines disease susceptibility and drug responses in African populations.

• Data generated from this effort will inform strategies to address health inequity and ultimately lead to health benefit in Africa.

Goals• Study and compare the DNA of 4,000 people whose physical

characteristics are well documented from previous studies, the project aims to identify those changes that have no noticeable effect and those that may be linked to a particular disease;

• By studying on 6,000 people and focusing on protein-coding areas, with extreme health problems and comparing them with the first group, it is hoped to find only those changes in DNA that are responsible for the particular health problems observed