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Learning outcomes
Link DNA with genes and gene structure
Understand the role of chromosomes in packaging genes Appreciate the diversity of chromosomes; their structure and function Familiarise yourself with jargon of the molecular content of the human genome
Overview of lecture
Revision of DNA structure and content Structure and function of genes Packaging of DNA onto chromosomes Structure and function of chromosomes Sex chromosomes
Mendelian factors - genes are located on chromosomes Not all chromosomes are equal in gene content Autosomes Variable number of genes X chromosomes gene rich Y chromosomes - gene poor
Composition of DNA
4 base pairs
Purines; Adenine and Guanine Double ring structure Pyrimidines; Cytosine and thymine
Genes: structure
Genes :
A locatable region of genomic sequence, corresponding to a unit of inheritance These are associated with regulatory, transcribed and other functional regions
Exon Intron
Codon Codon Codon Codon
Codon Codon Codon
Exon Intron
Exon
ATG TTA AGT CCT GAT GCC TAA AGG GCC TAT GTA TTC GAA TTC TAA TAG
Chromatin
Euchromatin Makes up the majority of the uncondensed chromosome Transcriptionally active Majority of the active genome Heterochromatin Remain condensed through out cell cycle Replicates later than rest of genome Usually transcriptionally inactive Two types Constitutional Facultative
Chromosome structure
Telemere
P Arm
Centromere
Q Arm
Sister chromatids
Chromosome diversity
Metacentric Submetacentric Acrotacentric Telocentric
Insertions
Translocations
Summary
Genes are packaged on to chromosomes Chromosomes are a heritable unit Karyotype analysis is based on the structure of a the genome Cytogenetics FISH Chromosomal mutation Sex chromosomes unique properties compared to the rest of the genome
http://www.ncbi.nlm.nih.gov/mapview/map_search.cgi?taxid=9606
Measuring DNA.
Base pair (bp) Kilobase pairs (kbp or kb) Subdivisions of chromosomes
Bases Sequences Contigs Scaffolds Super Scaffolds
chromosomes
Genomes
Chromosomes Genomes
Genes
Distribution varies greatly Few in heterochromatin, majority in sub telomeric euchromatin Made up of single copy genes and multigene families
Multigene families
Many genes have similar functions: gene duplication with subsequent evolutionary divergence Often found in clusters eg. Globin gene cluster on chromosome 16
Others widely dispersed throught the genome eg. Hox developmental genes.
Gene Superfamilies
Limited sequence homology but share functionality often having similar structural domains. Examples include the immunoglobulin genes which are almost certainly derived from duplication of a precursor gene.
Extragenic DNA
80,000 genes with an average size of 1015kb Account for only 25-35% of the human genome The remaining 70% is made up of repetative DNA sequences which are predominantly transcriptionally inactive.
Satelite DNA
10 -15% of human genome Simple short tandemly repeated DNA sequences Transcriptionally inactive Clustered around the centromeres of certain chromosomes Named after the characteristics of this type of DNA in density gradient centrifugation.
Minisatelite DNA
Two families of transcriptionally inactive repeated short DNA sequences Telomeric DNA
The end of telomeres contain 10-15kb of tandem repeats of a 6bp repeat sequence. Chromosomal integrity Telomerase
Minisatellite DNA
Hypervariable minisatelite DNA Highly polymorphic Short tandem repeats of a core sequence Polymorphism in repeat number is the basis for genetic fingerprinting (forensic/paternity) Often located close to telomeres
Microsatelite DNA
Single, di, tri, or tetra nucleotide repeats located througout the genome some trinucleotide repeats are associated with genetic diseases Highly polymorphic and are used to map genes
AAAAAAAAAA
TATATATATATAT
ATCATCATCATC GTTTGTTTGTTT
SINEs
5% of genomes consists of 750,000 copies of SINEs. Most common is a 300bp repeat which has similarity to a signal recognition particle involved in protein synthesis They are called Alu repeats Retrotransposons are genetic elements that can amplify themselves in a genome and are ubiquitous components of the DNA of many eukaryotic organisms.
LINEs
5% of genome Most common one is sequence of 6000bp that occur in about 100 000 copies which encodes a reverse transcriptase .
Mitochondrial DNA
Every cell has several thousand mitochondria Each mitochondria has its own 16.6kb circular double stranded DNA, mtDNA It has very little repetative DNA and codes for 37 genes Mitochondria are inherited exclusively from the oocyte
Summary
A variety of genes with a variety of functions 1 gene = 1 protein Majority of the genome is non coding Vast amounts of the genome is repetitive Mitochondrial DNA organelle, maternally inherited