Download introduction1

A quick course in genetics
part 1
by
Elísabet Einarsdóttir
[email protected]
7. Nov 2003
General outline
Cells
DNA, genes & chromosomes
RNA & transcription
Meiosis & mitosis
Mendel
Chromosome recombinations
Genetic & physical distances
Uses for genetics & genomes
Cells
DNA, genes & chromosomes
RNA & transcription
Meiosis & mitosis
Mendel
Chromosome recombinations
Genetic & physical distances
Uses for genetics & genomes
The basic structure of living organisms
- the cell
More cells
Plant cell
Bacterial cell
Cells
DNA, genes & chromosomes
RNA & transcription
Meiosis & mitosis
Mendel
Chromosome recombinations
Genetic & physical distances
Uses for genetics & genomes
Central dogma of information flow in genetics
DNA (dideoxynucleic acid)
– the double helix
The structure of DNA
A gene
A segment of DNA that is the template for
making a protein
Structure of a gene
regulatory
region
Region that acts as a template for
the production of proteins
Chromosomes
- the packing of DNA
The structure of a chromosome
Telomere
regions
Chromosome banding
p-arm of chromosome
(short arm)
q-arm of chromosome
(long arm)
p5
p4
p3
p2
p1
q1
q2
q3
q4
q5
q6
q7
E.g. linkage of a disease to 2q7.2
The human chromosome map
Chromosomal abnormalities
Downs syndrome –
3 copies of chr 21
Turner syndrome – only
one X chromosome
Cells
DNA, genes & chromosomes
RNA & transcription
Meiosis & mitosis
Mendel
Chromosome recombinations
Genetic & physical distances
Uses for genetics & genomes
Extracting genetic information from DNA
- making an RNA copy of DNA
DNA to RNA to protein via the ribosome
The splicing of RNA
DNA template
exon
intron
exon
intron
exon
intron
exon
Unspliced RNA copy of DNA
Ready-to-use mRNA
intron
exon
Alternative splicing of RNA
Different functions of different splice variants
Different expression of different splice variants
Dominant-negative variants
Amino acids
• Amino acids link together to form a long chain
• R (side chain) – varies between amino acids
• There are 20 different amino acids
Ribosomes translate 3-base sequences into
amino acid chains – the building blocks for proteins
amino acid chain
ribosome
AAGCUGAGAUCAGUUCGGAUACCGUA
Note: T in DNA becomes U in RNA
RNA “copy of DNA”
The importance of being in-frame
In-frame:
THE FAT CAT ATE THE BIG HAT
1 bp deletion: THF ATC ATA TET HEB IGH AT
1 bp added: THE FAT CCA TAT ETH EBI GHA T
3D structure of a protein
Cells
DNA, genes & chromosomes
RNA & transcription
Meiosis & mitosis
Mendel
Chromosome recombinations
Genetic & physical distances
Uses for genetics & genomes
Mitosis - a cell divides to make two
identical cells – part of normal growth
Meiosis – only during reproduction
Egg cells
from mother
Sperm cell
from father
An offspring
Half of the chr from
mother, half from
father
Cells
DNA, genes & chromosomes
RNA & transcription
Meiosis & mitosis
Mendel
Chromosome recombinations
Genetic & physical distances
Uses for genetics & genomes
Loci, alleles & markers
A locus is any point (or region) in the genome
A genetic marker is anything in the genome that is variable
and can be used to compare individuals
If a locus is variable, distinct alleles (forms) of the locus
(e.g. a gene or marker) can be defined and analyzed
A genotype is the set of alleles an individual
has at a particular locus
A phenotype is a visible trait in an individual (e.g. blue
eyes or the presence of a disease)
Gregor Mendel (1822-1884)
- the austrian monk with a passion for peas
•The law of segregation
Each individual carries two copies (alleles) of every
gene and only one of these is transmitted to each child
•The law of independent assortment
Alleles from unlinked loci are assorted independently
Mendel´s experiment with peas
S: smooth gene
s: mutated smooth gene
Punnet´s square:
½ Ss = smooth
¼ SS = smooth
¼ ss = Wrinkled
Principles of Mendelian analysis
-First law
• In each individual a trait is determined by two copies
(alleles) of the same gene, one paternal and one
maternal
• Only one of the two parental alleles is transmitted to
each child but with equal probability
Mother Aa
Father Aa
50% A
50% a
50% A
25%AA
25%Aa
50% a
25%Aa
25%aa
Principles of Mendelian analysis
- Second law
-The principle of independent segregation applies
independently to gene pairs determining different
traits
- Alleles from unlinked loci are assorted
independently
Aa
Bb
50% A
50% a
50% B
25%AB
25%aB
50% b
25%Ab
25%ab
Alleles from unlinked loci segregate
independently
Alleles from linked loci do not segregate
independently
Some points to note
• A child always inherits one copy of each chromosome
from each of the parents (meiosis, Mendel’s fist law)
• Any deviation from this can be pathogenic, e.g. Turner
syndrome (only one X) and Downs syndrome (3 copies
of chr 21)
• A girl has two X chromosomes (one from each parent),
a boy one X and one Y chromosome (X from mother, Y
from father) – implications for X-linked diseases
• Each chromosome is inherited independently of the
other one, which copy of a parents chromosomes the
child inherits is thus random (Mendel’s second law)
Cells
DNA, genes & chromosomes
RNA & transcription
Meiosis & mitosis
Mendel
Chromosome recombinations
Genetic & physical distances
Uses for genetics & genomes
Recombination of parental chromosomes
- a source of variation & essential for looking at
genetic distances & mapping disease
Recombination pattern in a family
Maternal grandparents
Parental grandparents
Father
Mother
Child
Some points on recombinations
• Recombinations happen only during meiosis
(during the generation of egg- or spermcells).
• Recombinations occur in each generation, usually
at least once per chromosome
• Recombinations are in theory random, but in principle
the likelyhood of recombinations at a particular point
in the genome is quite variable
• Almost no recombination at the centrimere, higher
frequency of recombinations closer to the telomeres
Cells
DNA, genes & chromosomes
RNA & transcription
Meiosis & mitosis
Mendel
Chromosome recombinations
Genetic & physical distances
Uses for genetics & genomes
Physical distance
- Mb
Physical maps can be divided into three general types:
chromosomal or cytogenetic maps, radiation hybrid maps,
and sequence maps.
• The lowest-resolution physical map is the chromosomal map,
based on the banding patterns observed by microscopy of stained
chromosomes.
• More detailed radiation hybrid maps are made by breaking the
chromosomes into small pieces. If two markers map to the same
small fragment they are likely to be close together.
• The highest-resolution physical map is the complete sequencing
of each chromosome in the genome
Physical maps at NCBI
Genetic distance
- cM
Centimorgan (cM): a unit of chromosome length, equals the
length of chromosome over which crossing-over occurs with 1
per cent frequency
A
a
B
b
A
b
Recombination between locus A and locus B
If 1% of meiosis result in recombinant chromosomes
=> 1cM between A and B
Genetic maps at NCBI
Cells
DNA, genes & chromosomes
RNA & transcription
Meiosis & mitosis
Mendel
Chromosome recombinations
Genetic & physical distances
Uses for genetics & genomes
Uses for genetics
Mapping disease
Genetic tests for known diseases
Microbial genomics
Forensics
Paternity tests
Development of medicines - pharmacogenomics
Breeding of animals and plants
Phylogenic studies & evolution
Human Genome Project
Aims: To generate a high-quality reference DNA sequence for the
human genome‘s 3 billion base pairs and to identify all human
genes.
Also to sequence the genomes of model organisms to interpret
human DNA, enhance computational resources to support future
research and commercial applications, explore gene function
through mouse-human comparisons, study human variation, and
train future scientists in genomics.
Founding partners:
U.S. Department of Energy
National Institutes of Health (NIH)
Wellcome Trust
As well as groups in Japan, France, Germany, and China
After the Human Genome Project
•The human genome consists of 3 billion bases (A, C, T, and G).
•The function of 50% of known genes is unknown.
•The human genome sequence is almost (99.9%) exactly the same
in all people.
• A human genome is 97% like a chimp genome, 75% of the mouse
genome
•Over 40% of the predicted human proteins share similarity with
fruit-fly or worm proteins.
•Chromosome 1 (the largest human chromosome) has the most
genes (2968), and the Y chromosome has the fewest (231).
The future of genetics?
The human genome
is like a book where each letter has been read, but
there are no chapters or page numbers so you
don’t really know what it all means or what to
make of it....