Genomics, genetic variation, and epidemiology

Question 1

what are genetic mutations

Answer 1

Genetic mutations are classed as changes to the DNA sequence that are passed from one generation to the next and so are heritable.

4 types of mutation: gain or loss of function, lethal mutations, ineffective mutations.

It is unpopular to say this word to patients as it comes with stigma, its better to say variant.

Question 2

Define: indel

Answer 2

where a nucleotide is added or removed from the DNA (insertions and deletions). This can change the reading frame, as well as the amino acid sequence- so the function of the resulting protein.

Question 3

Define: bioinformatics

Answer 3

Bioinformatics refers to the storage, analysis, annotation, and retrieval of genomic data from an electronic database.

Genome databases are created and constantly updated, and link details of gene structure, gene sequence variation and functional data to aspects such as protein structure and function but also health, disability and disease.

Question 4

DESCRIBE THE ROLE OF GENOMICS IN HEALTHCASE (20)

Answer 4

Genomics helps us improve the diagnoses of diseases with genetic linkage. This helps inform patients of their likelihood of developing a genetically linked disorder.

Role of Genomics refers specifically to the study of whole genomes rather than individual genetic traits. Genomics looks at the ’structure’ of the whole human genome. It involves identifying genes, mapping specific functions to those genes but also understanding the sequence variations across the genome. It also looks at where and when these genetic variations are linked to changes in gene function, especially those associated with human health and disease. As such genomics studies the evolution of the human genome and the significance of those evolutionary changes.

It has the potential to transform healthcare with more accurate diagnosis of a broader range of diseases with a genetic basis. It will also let people know their likelihood of developing one of these diseases.

Advances in technology has allowed us to obtain more data from DNA. By collecting DNA from a large amount of people, we will be able to understand genes more by comparing across groups of people, which will help in in understanding what is wrong for a patient. By linking health issues and diseases with specific genes or groups of genes we can identify risk factors and create more preventative healthcare programs.

Question 5

define genetics

Answer 5

refers specifically to the study of heritability. This is an area of science that describes how a genetic trait, such as eye colour or hair colour is passed on from parents to offspring.

Question 6

define genomics

Answer 6

the Structural and functional mapping of genomes and their evolution. We all have differences in our genome.

Question 7

define gene

Answer 7

‘Basic physical and functional unit of heredity’ (you pass on versions of your genes to your kids).
Many gene functions and gene interactions poorly understood. Genes encode proteins.

Question 8

describe post translational modification as a reason we have so many proteins

Answer 8

Changes the structure and function of the final protein by, Adding carbohydrate parts, Adding lipid parts, Modifying AA side chains, Adding chemical regulators. this can lead to a change of the overall function of a protein.

Question 9

describe alternate gene splicing as a reason we have so many protiens

Answer 9

this is where more than one protein can be made from part of a DNA strand. this is because within a gene, different exons (protein coding reigons) can be used. for example, there could be 6 exons on a gene, and the encoding of a protein might only have 4 of them, and a protein from the same gene might use them all.

Question 10

what is a pseudogene

Answer 10

non-functional gene - they used to be functional but they are no longer. It might lack a start codon or a premature stop codon, so the gene doesn’t work and produce a protein.

Question 11

what is a protein? what different types are there?

Answer 11

a chain of amino acids, which is determined by the DNA sequence of the protein-encoding gene.
There are 2 types: structural and functional proteins.
Structural proteins are responsible for the shape and structure of cells and tissues, such as collagen and elastin.
Functional proteins have biological activity, such as enzymes, neurotransmitters, and ion channels.

Question 12

what is an amino acid

Answer 12

a codon chain, which is made of only 3 nucleotides.

Question 13

what types of nucleotide are there

Answer 13

purines and pyrimidines, which are complementary pairs.

Question 14

what is a genotype

Answer 14

Someone’s complete set of genetic material including the various variant genes that they carry

Question 15

what is the role of cells in DNA

Answer 15

chromosomes hold together DNA, and histones hold together and regulate the genes within it.

Question 16

what does genetic linkage mean

Answer 16

– when a mutation has a link or impact on health conditions

Question 17

what is a somatic mutation

Answer 17

A somatic mutation describes any alteration at the cellular level in tissues, which occurs after fertilization. These mutations do not pass on to offspring. Somatic mutations are a normal part of aging and occur throughout an organism’s life cycle either spontaneously as a result of errors in DNA repair mechanisms or a direct response to stress

Question 18

what is epigenetics

Answer 18

the study of how gene activity can be controlled without changing the DNA sequence itself. Behavioural and environmental factors can cause epigenetic changes that affect the way genes work. Epigenetic changes are reversable, but can be heredited.

Question 19

what is the epigenome

Answer 19

= an important factor in the control of the production of genes. It helps us switch on and off genes, and so helps control what proteins are produced

Question 20

EXPLAIN HOW GENE SEQUENCES CAN BE STORED IN DNA (20)

Answer 20

The backbone of the double helix is made of sugary molecules, and the connections between the 2 helix are base pairs, which are bonded together to form a code that the cell follows to make proteins- this is all within the chromatin of the nucleus of a cell. Base pairs are nucleotides that bond together. For example, the purine nucleotide A pairs with the pyrimidine nucleotide T (or U in RNA); the same way as G pairs with C.

From the DNA, we have a transcriptional process to produce RNA. This happens in the nucleus of the cell, where the DNA is pulled into single strands with a U base. Introns are removed so there is only exons. There is also a translation process, where RNA is used as a template to form the amino acids needed to make a protein.

RNA is read 3 letters at a time- the codon UAG is used to stop the translation process, and the codon AUG tell it to start. There are 20 amino acids that are used to make proteins in the body, each have different chains of nucleotides and this impacts their function. We know the sequences of many genes, but many are still poorly understood.

Question 21

EHY DOES GENETIC VARIATION OCCUR

Answer 21

Genetic variation can be caused by sexual reproduction, random, events, or mutagens.

Variation caused by sexual reproduction is heritable, and is caused by genetic recombination events. Random genetic variation is not heritable as it happens during normal cell division or during the life of a cell, and it is usually inappropriate DNA repair mechanisms following any damage. Mutagens are things that cause mistakes in genetic coding. They can be pollutants / environmental triggers, viral insertions (viruses insert their own dna into our cells) or even radiation.

Question 22

WHAT IS EPIGENETIC TAGGING (20)

Answer 22

Epigenetic tags = They are physical chemicals in the cells of our body that change how the DNA works.

One way epigenetics works is by chemicals being added to the DNA, which is called methylation. This is where the C nucleotides have a chemical tag attached to it, and if enough of the C nucleotides in the gene are methylated then the gene can be switched off.

Epigenetic factors can also bind to histones, which alters the extent to which DNA can wrap around it. This changes the availability of the gene to be activated because the gene wont be able to unwrap and be transcribed as well.

Environmental factors and behaviours can rigger epigenetic changes. Changes in how we use our genome such as stress, smotking, and exercise change the way genes are switched on and off- so alters gene activation. Some epigenetic tags are heritable and remain on the genome.

Question 23

HOW DO WE HAVE MANY TYPES OF PROTEIN

Answer 23

there are 2 ways we have many types of protein: alternate gene splicing and post translational modification.

alternate gene splicing: from one gene, it can encode for more than one protein because the proteins can be made from different exons (protein coding reigons) within the gene.

post translational modification: this is where the body can change the overall function of a protein by adding carbodydrate or lipid parts, chemical regulators, or modifying amino acid side chains

Question 24

GENETIC TESTING in terms of deletion varients

Answer 24

the physical size of a gene gets smaller if a mutation causes the coding to get deleted. so, we can take a blood sample and compare a ‘normal’ gene coding to a possible mutated one. this is a way of checking for a mutation (checking the length of the gene). eg instead of 63 base pairs they might have 60.

however, for this kind of testing you need to know the gene involved in a disease, when we don’t really know all the genes involved in most illnesses.

Question 25

TYPES OF GENE VARIENT (20)

Answer 25

Benign gene variants are those that have not been associated with disease. With further research, it is possible in the future for them to be associated with disease, but this is not the case with current research. A link might never be made because a variant might not have any negative effects on the functioning of a gene, or the effects might be so insignificant that it doesn’t change the functioning of the gene enough to have a bad effect on the body. The reason this point is important is because some we haven’t determined the genetic linkage of some diseases yet, and we still no not understand all genes.

Pathogenic gene variants are associate with disease. The gene has been identified and linked to a disease, and details of specific variations in the genetic code have been described. The protein for the identified gene clearly functions in a different way, for example, there may be a gain or loss of function.

Loss of function variant - gene product (the protein) loses some, or all its function. For example, if there was a change in the coding sequence that corresponded to a change in amino acid sequence this may negatively impact the functioning of the final gene product (protein).

Gain of function variant - new or enhanced activity for gene product. For example, if there was a change in the coding sequence that corresponded to a change in amino acid sequence this may positively impact the functioning of the final gene product (protein) leading to an enhancement of it’s normal function or the addition of a new functional characteristic.

Question 26

MECHANISMS CREATING GENE VARIENTS (20)

Answer 26

Single nucleotide variants – missense and nonsense mutations. a missense mutation is where a nucleotide has been substituted for a different one, which could create a different amino acid, which could therefore create a different protein. however, a nonsense mutation is where a single nucleotide has been substituted for a stop codon, so the resulting protein could be partially or completely not functioning.

Indels – this is where a nucleotide is added or removed (insertions or deletions). This can cause a change in the amino acid sequence, so a change in the resulting protein. It can also cause the reading frame to move so you are reading the wrong sequence. a deletion can cause the reading frame to move, which is called a frameshift varient.

Structural variants- there are 4 types : translocations, inversions, large deletions, and copy number variants. Translocations is where large chunks of a chromosome being removed and replaced. inversions is where part of a chromosome is cut out and put back in backwards. large deletions are where large chunks of the chromosome are deleted by accident. copy number varients are where there are a large amount of copies of a gene in a chromosome, this can cause too much of a protein to be produced.

Repeat variants – where a gene produce too much of a protein, which blocks neurons in the NS and causes reductions in motor control.

Question 27

what is mitosis

Answer 27

a process of cell reproduction where one cell divided into 2 identical cells

Question 28

what is meiosis

Answer 28

where a single cell divides twice to produce four cells containing half the original amount of genetic information. These cells are our sex cells – sperm in males, eggs in females.

Question 29

what is an exon

Answer 29

a protein coding reigon on a gene

Question 30

what is an intron

Answer 30

non coding reigon of a gene

Question 31

what is a benign gene varient

Answer 31

Benign gene variants are those that have not been associated with disease. With further research, it is possible in the future for them to be associated with disease, but this is not the case with current research. A link might never be made because a variant might not have any negative effects on the functioning of a gene, or the effects might be so insignificant that it doesn’t change the functioning of the gene enough to have a bad effect on the body. The reason this point is important is because some we haven’t determined the genetic linkage of some diseases yet, and we still no not understand all genes.

Question 32

what is a pathogenic gene varient

Answer 32

Pathogenic gene variants are associate with disease. The gene has been identified and linked to a disease, and details of specific variations in the genetic code have been described. The protein for the identified gene clearly functions in a different way, for example, there may be a gain or loss of function.

Question 33

what is a loss of function gene varient

Answer 33

Loss of function variant - gene product (the protein) loses some, or all its function. For example, if there was a change in the coding sequence that corresponded to a change in amino acid sequence this may negatively impact the functioning of the final gene product (protein).

Question 34

what is a gain of function gene varient

Answer 34

Gain of function variant - new or enhanced activity for gene product. For example, if there was a change in the coding sequence that corresponded to a change in amino acid sequence this may positively impact the functioning of the final gene product (protein) leading to an enhancement of it’s normal function or the addition of a new functional characteristic.

Question 35

mechanisms - what is a single nucleotide varient (2 types)

Answer 35

Single nucleotide variants – missense and nonsense mutations. a missense mutation is where a nucleotide has been substituted for a different one, which could create a different amino acid, which could therefore create a different protein. however, a nonsense mutation is where a single nucleotide has been substituted for a stop codon, so the resulting protein could be partially or completely not functioning.

Question 36

mechanisms - what is an indel (2types)

Answer 36

Indels – this is where a nucleotide is added or removed (insertions or deletions). This can cause a change in the amino acid sequence, so a change in the resulting protein. It can also cause the reading frame to move so you are reading the wrong sequence. a deletion can cause the reading frame to move, which is called a frameshift varient.

Question 37

mechanisms - what is a structural varient

Answer 37

Structural variants- there are 4 types : translocations, inversions, large deletions, and copy number variants. Translocations is where large chunks of a chromosome being removed and replaced. inversions is where part of a chromosome is cut out and put back in backwards. large deletions are where large chunks of the chromosome are deleted by accident. copy number varients are where there are a large amount of copies of a gene in a chromosome, this can cause too much of a protein to be produced.

Question 38

mechanisms - what is a repeat varient

Answer 38

Repeat variants – where a gene produce too much of a protein, which blocks neurons in the NS and causes reductions in motor control.