2d Genetics Flashcards
What are the basics of genetics?
All your genetic information is contained in DNA - almost everything about your physical being, like the color of your eyes, the shape of your nose, even your likelihood of getting certain diseases is determined (at least in part) by your DNA.
How does your DNA do this? All of these physical characteristics are manifested through proteins your body makes, and DNA is like a blueprint for these proteins. The plan to make one single protein (or sometimes one group of proteins) is called a “gene.”
When one of your cells wants to make a protein, the process begins at the DNA, which is in the nucleus. First, the appropriate gene is found and a template of the gene is created. This blueprint/template is called mRNA, or messenger RNA.
The mRNA then moves out of the nucleus to the construction site - the ribosome. In the ribosome, the mRNA template is read and a protein is built from specific building blocks called amino acids. That’s how a protein is put together.
There are other kinds of RNA - mRNA is just one. Ribosomes are partially made of RNA called ribosomal RNA or rRNA. And small RNAs are used to read the mRNA - they are called transfer RNAs or tRNAs and are like the individual construction workers who build each block.
What are the different types of DNA?
The same thing but categorised on where it is stored inside the cell, most is in the nucleus (nuclear DNA) but a small part is in the mitochondria (mitochondrial DNA).
Nuclear DNA - Wound up and packaged with proteins to form structures called chromosomes. Humans have 23 pairs of chromosomes in each cell (46 chromosomes in total). Twenty-two of these pairs are very similar to each other in size and shape, termed the autosomes. One member of each pair is inherited from the mother while the other is inherited from the father. Additionally, humans have a pair of sex chromosomes. Females have two X chromosomes while males have one X and one Y. A karyotype is a species-specific characteristic set of chromosomes.
Mitochondria DNA has a specific role in cell’s energy metabolism. It is found outside of the nucleus in mitochondria and is all inherited from an individual’s mother.
What are the roles of DNA?
1) To be reproducible, enabling maintenance and growth of cells and reproduction
1) Encode proteins or RNA
What is genomics?
A gene is a sequence of nucleotides that codes for a specific protein or RNA.
Genomics is the term for the study of all the genes in an individual.
What is genomics?
A gene is a sequence of nucleotides that codes for a specific protein or RNA.
Genomics is the term for the study of all the genes in an individual.
How is the human genome formed?
Within the human genome, there are 3 million base pairs and ~20-25,000 genes.
The sequence of a set of three bases is called a codon; each of these codes for a specific amino acid which then form the building blocks for proteins.
Genes contain protein coding sequences (exons) and non-coding sequences (introns), with only 2% of DNA made up of exons.
What is the process of protein production?
Genes are responsible for encoding proteins in an organism, with each gene coding for one polypeptide, a chain of amino acids. These polypeptides then become proteins after folding to become a functional three-dimensional form. The stages in protein production are as follows:
a) Transcription
The DNA sequences of the gene acts as a template to produce ribonucleic acid (RNA). RNA is similar to DNA but has a slightly different sugar making up its backbone (ribose vs. deoxyribose), is single stranded and has the base uracil (U) instead of thymine (T).
b) Splicing
Introns, the non-coding sequences, are removed from the RNA.
c) Exporting
Unlike DNA, RNA is able to leave the nucleus of a cell and is exported. This type of RNA is termed messenger RNA.
d) Translation
Messenger RNA is used to direct the assembly of a specific protein chain through production of amino acids. These are then joined together to produce a peptide in the ribosome (a molecule in every cell where protein synthesis takes place which is comprised of ribosomal RNA and ribosomal proteins). RNA involved in transferring amino acids to the polypeptide chain is termed transfer RNA.
e) Protein modification
Peptides will assemble together to form a protein which will involve folding as it is functional only in three-dimensional form.
f) Translocation
The final stage involves moving the protein to where it is needed in the cell.
What is the difference between a genotype and phenotype?
The set of alleles a person has is known as their genotype. This genotype then codes a set of observable characteristics which are then expressed, known as the phenotype.
What is variation in genetics?
There are two types of cell division. Mitosis results in the production of two cells each with the same number and type of chromosomes as the parent cell which is typical of ordinary tissue growth. Meiosis is the process of cell division resulting in the production of gametes (sex cells).
Each gamete contains one set of chromosomes (23 single chromosomes instead of 23 paired sets of chromosomes). Gamete production can result in variation. During the process of sexual reproduction, genes are shuffled, resulting in different genetic combinations and variation in offspring.
What is a mutation?
Mutations are rare changes in the sequence of DNA that can result in variation. Most mutations are generally harmful, but some can improve the organism’s ability to survive and reproduce, forming the basis of evolution by natural selection. Mutations most commonly result from mistakes made when DNA is being replicated during cell division. During mitosis, mutations are normally due to natural events such as replication errors or cosmic radiation, though they can result from environmental hazards such as man-made radiation or exposure to mutagenic chemicals. Most of these alterations are repaired but if not, they can lead to changes in a protein that can result in genetic disease. When mutations occur in the gametes, they are passed on to the next generation.
Such mutations can be small scale or large scale.
While small scale mutations usually only affect a single protein, it can have significant consequences.
In what ways can inherited genetic diseases at birth be caused?
Genetic disorders are relatively common, with a combined prevalence of around 1-2% in the UK.
Some 4,000 inherited diseases are known to be associated with mutations in single genes, with recognisable patterns of inheritance. These are classified according to the chromosome on which they are found: autosomal, X-linked or Y-linked .
Some genetic diseases at birth can be chromosomal with variation in the number inherited. An example of this is Down syndrome, in which there is an extra copy of chromosome 21. Occasionally changes in the number of sex chromosomes can be inherited. In most cases, this has no noticeable impact, but females with only one X chromosome have Turner syndrome while males with an extra X chromosome have Klinefelter syndrome.
Alternatively, there can be structural abnormalities. An example is Cri-du-Chat syndrome resulting from a deletion on the short arm of chromosome 5 and Jacobsen syndrome, also called the terminal 11q deletion disorder. Some of these chromosomal changes are heritable.
In what ways does genetics explain familial risk of diseases?
Subsets of common disease that develop later in life can be prevalent in several members of the same family and the disease shows a recognisable Mendelian inheritance pattern associated with a single gene. These single gene subsets of common disease typically account for a maximum of ~5% of the total burden of disease. An example is familial hypercholesterolemiaor a mutated BRCA1/BRCA2 gene.
Other diseases can be associated with other specific genetics variations that are not just a single mutation. These may increase the risk but do not absolutely predict occurrence, such as coronary heart disease (e.g. VAMP8 variant), diabetes (e.g. PCSK9 variant) and cancer (e.g. rs4143094 variant for bowel cancer).
Apart from these specific cases, the majority of diseases can be affected by both inherited and environmental/lifestyle factors. These diseases are termed multifactorial and account for the majority of genetic disorders, outnumbering the number of single gene disorders. There may be multiple genes involved which may interact with each other, with environmental factors and with lifestyle factors. The association, therefore, is often not clear and difficult to disentangle.
It should be noted that most genetic alterations that lead to cancerous behaviour arise in the individual and do not affect the germline (the genomic material that is heritable).
What is Epigenetics?
The study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself.
These changes occur from environmental exposures such as chemicals, tobacco smoke, nutrition and stress.
This is a rapidly expanding field, with the understanding that both the environment and individual lifestyle can directly interact with the genome to influence epigenetic change
What are Monogenic disorders (Medndellian Disorders)?
Autosomal Recessive
Autosomal Dominant
Sex-Linked
Mitochondrial
What is an Autosomal Recessive condition, give an exmaple?
In autosomal recessive conditions, the individual develops the disease only if they inherit two copies of the mutant allele. They must therefore inherit a copy from each parent. If the child only inherits one copy, then they will be a carrier, but will be phenotypically normal.
A carrier has a 50% chance of passing on the mutant allele to each child. If both parents are carriers, then there is a 25% chance of the child inheriting both copies and being born with the disease.
Examples of autosomal recessive conditions include cystic fibrosis and sickle cell anaemia.
What is an autosomal dominant condition, give an example?
In autosomal dominant conditions, an individual can develop the disease with either one or two copies of the mutant allele.
There is, therefore, no carrier state as all those with the gene have an abnormal phenotype.
A person with one parent who has the disease has a 50% chance of inheriting the mutant gene.
Examples of autosomal dominant conditions include Huntington’s disease.
What are sex-linked disorders?
Sex-linked disorders occur when the gene associated with the disease is on one of the sex chromosomes, almost invariably the X-chromosome.
They are usually inherited recessively. Women are more likely to be carriers of X-linked recessive conditions by nature of having two X-chromosomes and men are more likely to develop disease.
All daughters of affected men are therefore carriers and no sons are affected due to inheriting the Y chromosome.
When a women is a carrier, her daughters have a 50% chance of becoming a carrier.
Examples of sex-linked disorders include Duchenne muscular dystrophy and haemophilia.
What are mitochondrial linked genetic disorders?
Mitochondrial genetic conditions are maternally inherited, with mutations typically resulting in energy deficiency in cells as seen with Leigh’s disease.
There is no predictable inheritance pattern and the severity of mitochondrial diseases can vary according to the proportion of mitochondria that carry the mutation.
This is known as the threshold effect – a certain proportion of mutated mitochondrial DNA is required to be inherited for the individual to develop symptoms of the disease.
What are polygenic disorders?
Polygenic disorders are caused by several gene variants, each affecting susceptibility to disease (as opposed to monogenic disorders which are cuased by a single mutaiton).
There is increasing evidence to suggest strong genetic components to disorders not previously thought to be genetic and they are, therefore, likely to be common in the population, much more so than single gene disorders. Examples of diseases influenced by many genes include cancer, coronary heart disease and diabetes.
However, due to complex inheritance patterns, it can be difficult to identify these genes.
What are chromosomal disorders?
Chromosomal disorders can result from numerical or structural abnormalities in chromosomes and can be inherited or appear de novo, with the latter generally more common.
Microscopic techniques are available to assess the number and structure of chromosomes (e.g. Down syndrome), with a karyotype used to provide an organised picture of a person’s chromosomes.
The abnormalities usually result from an error in cell division, either in mitosis (where identical copies of the original cell are produced) or in meiosis (where gametes are produced), If they occur in the gametes then the abnormality will be present in every cell in the offspring, while if they happen after conception then only some cells will have the abnormality.
Factors can increase the risk of this happening, such as increasing maternal age and environmental factors.
What is genetic penetrance and how does it relate to each type of gene mutation that can cause disease?
The penetrance of a genetic condition is the likelihood that a person carrying a disease-associated genotype will develop the disease.
Single gene disorders have high penetrance; both Huntington’s disease and cystic fibrosis are near 100% penetrant by the age of 70 and at birth respectively, meaning all affected individuals will develop the disease.
For those mutations which increase the risk of developing a disease, the risk is time-dependent, increasing over time. Mutations in the BRCA1 gene that are associated with familial breast cancer have a lifetime prevalence of 60-85%.
Polygenic disorders tend to have low penetrance, with the likelihood of developing the disease affected by the modifying effects of other genes and/or environmental factors.
How do genes and the environment interact to cause disease?
Most genetic disorders are multifactorial; they result from a complex interplay between inherited mutations in multiple genes, often interacting with environmental factors.
The susceptibility to developing disease such as heart disease and diabetes can increase following exposures such as infections, chemicals, physical hazards, nutritional exposures and behaviours. An example is phenylketonuria: in the absence of dietary phenylalanine, no disease develops.
Which type of studies can be used to assess whether a disease is passed on through a genetic component?
Family studies:
Family studies can be used to determine initially if there is a genetic component to a disorder. If there is a higher risk of disease in family members of an affected person than in the general population, this suggests a genetic component.
Linkage Studies:
Linkage analysis is a statistical method for mapping the genes for heritable traits to their chromosome locations. Genome-wide markers are tested in pedigrees segregating a trait. The statistical method of linkage analysis combines these data to identify chromosome regions likely to harbor genes for the trait.
Association studies identify specific genes by measuring the relative frequency with which a specific polymorphism occurs with a disease of interest in the population. For example, genes encoding the cell-surface receptor molecule CCR5 have been shown to be associated with increased resistance to infection by HIV, and polymorphisms encoding the major histocompatibility complex play a major role in immune response to pathogens.
Genome-wide association studies look at genetic variants across the whole genome in different individuals to see if any variant is associated with a particular trait. These types of studies can find genetic variations that contribute to common complex diseases such as mental illness and asthma. Two groups of people provide DNA, one with the disease and one without the disease, provide DNA and markers of genetic variation, single nucleotide polymorphisms, are sought. If these are more common in the group with the disease, the variations are said to be associated with the disease, although they may not directly cause the disease. Further sequencing work is needed to identify the exact genetic change.
What is the inheritance pattern of the 4 following pedigrees?
1) Autosomal Dominant
2) Autosomal Recessive
3) X-Linked Dominant
4) X-Linked Recessive
What are the functions of genetic testing?
Diagnose a genetic disorder
Predict the likelihood of future disease occurrence
Facilitate disease management through personalised treatment
Assist with primary and secondary disease prevention
Can assess whether family members are at risk
