Cancer genetics: Lecture 3.
Human genome: Is all the genetic information in a human (all the genes and the
spaces in between). The human genome is in the nucleus of every cell except from
rbc which don’t have a nucleus. We have 46 chromosomes, 44 of them are called
autosomes and 2 are called sex chromosomes. The human genome project
identified every chemical base in the genome and discovered that there are 19.000 –
20,000 protein coding genes. The genes that are not coding for proteins and
encoding for microRNA. The genome size is approx. 3200 mega base pairs.
Human karyotype:
we have 23 pairs, male karyotype contains x and y, female contains xx.
A human karyotype is a display of its genome. It shows all the
chromosomes present in an individual after they have been stained and
arranged in pairs called homologs.
The centromere of a chromosome is the region that separates the two
arms. The arm above the centromere, which is shorter, is called the p
arm, while the longer arm is the q arm.
- The 25,000 genes scattered throughout the human chromosomes make up
only about 3% of the total genome.
- While all the component bases in a gene are copied as information leaves the
nucleus, not all this information is kept. This is because within a gene there
are both coding and non-coding based. For example, in split genes, exons
provide the genetic instructions that are copied to direct protein building.
- These sections are preserved, but other noncoding sections within the gene,
(introns), are rapidly removed and degraded.
- There is a regulatory sequence of DNA close to each gene, which is able to
turn the gene off and on. Farther away there are enhanced regions, which can
speed up a gene’s activity.
DNA and chromosome structure:
- Chromosomes are made of DNA, which contains 4 bases that are adenine,
thymine, cytosine and guanine, there are approx. 3.2 billion chemical bases in
the human genome.
- Genes mRNA protein.
A gene encodes for mRNA, base pairing is used to transfer a genes information
from DNA to mRNA. mRNA and DNA can be distinguished, because in DNA the
adenine matches with a new base called uracil in the mRNA. mRNA travels from
the nucleus, to the cytoplasm and to ribosomes where translation occurs make
a protein.
, Within the nucleus of the cell the genes are transcribed to RNA, RNA processing
occurs, where the genes are spliced, introns are removed and mature RNA gets
translated into proteins in the cytoplasm.
A codon is made up of 3 mRNA nucleotides, there are 64 codons in total.
The codon AUG encodes for methionine and it starts translation in all proteins, 61
codons encode for 20 amino acids e.g. GCC, GCG, GCA encodes for alanine. There
are 3 codons which stop protein translation which are UAA, UGA, UAG There will be
multiple stop codons one after another.
Mutation is a change in the normal base pair sequence, its commonly used to define
DNA sequence changes which alter the protein function; however, some mutations
can also be silent. Most cancers arise from several mutations that occurs over a
lifespan.
Mutations
Somatic mutations:
Occurs in non-germline tissues, Germline mutations
and they are non-inheritable. E.g. Mutations that are present in the egg or sperm so all
mutation in the breast cells. the cells of the offspring are affected, they are
therefore inheritable, can cause cancer family
syndromes.
Tumours are clonal. They acquire
multiple mutations, a pancreatic tumour has approx. 64 mutations, and they keep
acquiring them as their genome is instable.
The cell begins to rapidly divide and forms a clone.
Tumours are evolving very quickly, so not all the local/ distant metastasis has the
same genome as the parent clone, as they have to evolve in different circumstances,
so they change their genetic information.
Genes are mutated differently in the different parts of the
pancreas. Based on the spectrum of mutations, it would be easy
to see for example a particular metastatic deposit would have
originated in the primary tumour.
There were some mutations in the metastatic deposits that were
not present in the primary tumour, so the tumour had evolved.
Different types of tumours.
Benign tumours (non-cancer) grow locally and they can’t spread through invasion
Human genome: Is all the genetic information in a human (all the genes and the
spaces in between). The human genome is in the nucleus of every cell except from
rbc which don’t have a nucleus. We have 46 chromosomes, 44 of them are called
autosomes and 2 are called sex chromosomes. The human genome project
identified every chemical base in the genome and discovered that there are 19.000 –
20,000 protein coding genes. The genes that are not coding for proteins and
encoding for microRNA. The genome size is approx. 3200 mega base pairs.
Human karyotype:
we have 23 pairs, male karyotype contains x and y, female contains xx.
A human karyotype is a display of its genome. It shows all the
chromosomes present in an individual after they have been stained and
arranged in pairs called homologs.
The centromere of a chromosome is the region that separates the two
arms. The arm above the centromere, which is shorter, is called the p
arm, while the longer arm is the q arm.
- The 25,000 genes scattered throughout the human chromosomes make up
only about 3% of the total genome.
- While all the component bases in a gene are copied as information leaves the
nucleus, not all this information is kept. This is because within a gene there
are both coding and non-coding based. For example, in split genes, exons
provide the genetic instructions that are copied to direct protein building.
- These sections are preserved, but other noncoding sections within the gene,
(introns), are rapidly removed and degraded.
- There is a regulatory sequence of DNA close to each gene, which is able to
turn the gene off and on. Farther away there are enhanced regions, which can
speed up a gene’s activity.
DNA and chromosome structure:
- Chromosomes are made of DNA, which contains 4 bases that are adenine,
thymine, cytosine and guanine, there are approx. 3.2 billion chemical bases in
the human genome.
- Genes mRNA protein.
A gene encodes for mRNA, base pairing is used to transfer a genes information
from DNA to mRNA. mRNA and DNA can be distinguished, because in DNA the
adenine matches with a new base called uracil in the mRNA. mRNA travels from
the nucleus, to the cytoplasm and to ribosomes where translation occurs make
a protein.
, Within the nucleus of the cell the genes are transcribed to RNA, RNA processing
occurs, where the genes are spliced, introns are removed and mature RNA gets
translated into proteins in the cytoplasm.
A codon is made up of 3 mRNA nucleotides, there are 64 codons in total.
The codon AUG encodes for methionine and it starts translation in all proteins, 61
codons encode for 20 amino acids e.g. GCC, GCG, GCA encodes for alanine. There
are 3 codons which stop protein translation which are UAA, UGA, UAG There will be
multiple stop codons one after another.
Mutation is a change in the normal base pair sequence, its commonly used to define
DNA sequence changes which alter the protein function; however, some mutations
can also be silent. Most cancers arise from several mutations that occurs over a
lifespan.
Mutations
Somatic mutations:
Occurs in non-germline tissues, Germline mutations
and they are non-inheritable. E.g. Mutations that are present in the egg or sperm so all
mutation in the breast cells. the cells of the offspring are affected, they are
therefore inheritable, can cause cancer family
syndromes.
Tumours are clonal. They acquire
multiple mutations, a pancreatic tumour has approx. 64 mutations, and they keep
acquiring them as their genome is instable.
The cell begins to rapidly divide and forms a clone.
Tumours are evolving very quickly, so not all the local/ distant metastasis has the
same genome as the parent clone, as they have to evolve in different circumstances,
so they change their genetic information.
Genes are mutated differently in the different parts of the
pancreas. Based on the spectrum of mutations, it would be easy
to see for example a particular metastatic deposit would have
originated in the primary tumour.
There were some mutations in the metastatic deposits that were
not present in the primary tumour, so the tumour had evolved.
Different types of tumours.
Benign tumours (non-cancer) grow locally and they can’t spread through invasion
