Chapter !1 - Introduction to Genomics Code : KSI0010

<Index of Chapter 1>

The human genome

Phenotype = Genotype +Environment + Life history + Epigenetics

Genotype is DNA sequence both nuclear and mitochondrial. 

Phenotype is the collection of your observable traits other than your DNA sequences. 

Life story includes the integrated total of your experiences and the physical and psychological environment in which you developed. 

At the interface between the genome and life experience are epigenetic factors. 

A genome is like a page of printed music. The page is a fixed physical object, but the notes are consistent with realizations, in time and space, in a variety of ways.

- a limited variety of ways. 

 

Contents of the human genome

Francis Crick encapsulated this scheme in the Central Dogma of Molecular biology. 

DNA makes RNA makes Protein.

The most prominent and familiar asepects of the genome, the regions that code for proteins. Protein coding genes are transcribed into messenger RNA(mRNA).

After processing, ribosomes translate mature mRNA to polypeptide chains. 

Some regions of the genome encode non-protein coding RNA molecules( that's RNAs exclusive of messenger RNAs), including but not limited to transfer RNAs, the RNA components of ribosomes and microRNAs and small interfering RNAs that regulate translation.

Other regions contain binding sites for ligands responsible for regulation of transcription. In assessing the total amount of the genome dedicated to control, one would need to include both the regulatory sites themselves, and all the proteins and RNAs encoded that have regulatory functions, arguably including receptors. 

 

 

Genes that encode the proteome

Proteome- that is the amino acid sequences of the proteins expressed. However, several mechanisms introduce additional variety into the genome - protemeome relationship.

In eukaryotes, a mechanism of generating variety from a single gene sequence is alternative splicing. Alternative splicing involves forming a mature from a gene, but always in the order in which they appear in the genome. 

In both prokaryotes and eukaryotes, RNA editing can produce one or more proteins for which the amino-acid sequence may differ from that predicted from the genome seuqnce. 

The leap from the one-dimensional world of sequences to the three dimensional world we inhabit.

DNA sequence determines protein sequence.

Protein sequence determines protein structure

Protein structure determines protein function.

 

Varieties of genome organization

Chromosomes. organlleles, and plasmids. 

The most general classification of cells, according to both their structure and molecular biology, divides prokaryotes, simple cells without a nucleus, from eukaryotes, cells with nuclei.

In a eukaryotic cell, most of the DNA is sequestered in the nuclesus. The nucleus is the site of DNA replication and RNA synthesis in gene transcription. 

Genes -As they come off the sequencing machines, genomes are long strings of As, Ts, Cs, Fs withous captions or sign posts. 

Protein coding regions

Some regions are expressed as non- protein coding RNA

Other regions are targets of regulatory interactions

Dynamic components of genomes

-Transposable elements

-Retrotransposons

-Transposons

-LINES and SINES

 

 

Genome sequencing projects

Many genome projects target individual species. In addition, a major component of public DNA sequence data repositories comes from metagenomic data. These are sequences determined from environmental samples, without isolating indicidual organisms. 

Genome projects and the development of our current information library

High-throughput DNA sequencing - single end reand & paired end read

-High throughput sequencing

-De novo sequencing 

-Resequencing

 

Variations within and between populations

-Cancer genome sequencing 

Healthy cells do accumulate mutations at a modest rate. Cancer cells that have lost checks on acuracy of DNA replication accumulate mutations copiously.

To distinguish variations arising from the disease it's preferable to compare the seuquences from same individual

 

Human genome sequencing

SNPs( Single nucleotide polymorphisms)

Haplotpyes

 

The human genome and medicine

Prevention of disease

Detection and precise diagnosis

EX. Huntington's disease

Discovery and implementation of effective treatment

Health care delivery

 

 

The evolution and development of databases

Sources of biological data include several high- throughput streams including

- Systematic genome sequencing 

- Protein expression patterns

- Metabolic pathways

- Protein interaction Patterns and regulatory networks. 

_ The scientific literature, inclding bibliographcial databases. 

Datavank evo-devo

Genome browsers. 

 

Protein evolution : Divergence of sequences and structures within and between species

Different globins diverged from a common ancestor

 

Ethical, lega and social issues

Databases containing human DNA sequence information. 

-DNA sequence databases, law enforcement and the courts (Samples)

Ethical considerations for compiling DNA databases. 

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