Genetics Flashcards
The genetic code for every feature of each human is contained where?
Within the nucleus of each cell of the body.
On what molecule is the genetic code is contained within a long string of nucleotides on?
The genetic code is contained within a long string of nucleotides on a molecule called deoxyribonucleic acid (DNA).
Each gene is the result of what?
Each gene is the result of a string of DNA that contains the instructions for how to form specific proteins. These proteins are responsible for how our body functions.
DNA codes for hundreds to thousands of genes are bundled into individual chromosomes - what are chromosomes?
Chromosomes are single molecules of DNA.
Chromosomes come in pairs.
Therefore, each human has two copies of each gene, one on each chromosome in a pair. One chromosome in each pair comes from each parent.
We have 23 chromosome pairs or 46 chromosomes in total.
Sex chromosomes vs-non sex chromosomes
One of the pairs of chromosomes are the sex chromosomes. The sex chromosomes are the X chromosome and the Y chromosome. Males have an X and a Y chromosome and females have two X chromosomes. The other 44 chromosomes are called autosomes. They are the non-sex chromosomes.
What is a genotype?
Genotype refers to the genes that we have. For example, having the gene that codes for brown eyes.
What is a phenotype?
Phenotype refers to the physical expression of the genes that we have. For example, actually having brown eyes.
A person’s DNA is the result of half the genes from their mother combined with half the genes from their father.
A mother’s egg contains half her DNA, and a father’s sperm contains half his DNA. The DNA that makes up the egg or sperm is selected at random and is impossible to predict. The process of creating a gamete (egg or sperm) that contains half the genetic material of a normal cell is called what?
Meiosis
What is the pincipal of Mendelian inheritance?
When there is a single gene that codes for a physical feature, the phenotype is the result of the combination of the two genes (one on each chromosome). Some genes are more dominant than others, and the phenotype will reflect the more dominant gene. This is called Mendelian inheritance.
Dominant vs recessive genes
Genes that are more dominant over other genes are known as dominant, and genes that aren’t expressed when paired with more dominant genes are called recessive.
Some genetic conditions exhibit a simple inheritance pattern called Mendelian Inheritance - what does this mean?
This type of inheritance only occurs where the disease is caused by a single abnormal gene on one of the non-sex chromosomes (i.e. not the X or Y chromosomes).
These chromosomes are called “autosomes”.
Potential outcomes of inheritance of a autosomal recessive condition when two parents are carriers?
The children of these parents have a 1 in 4 (or 25%) chance of having the disease, and 2 in 4 (or 50%) chance of being a carrier and a 1 in 4 (or 25%) chance of having normal genes.
When one parent has an autosomal recessive disease, and the other parent is a carrier, what are the chances of their children inheriting the condition?
The children of these parents have a 50% chance of having the disease and a 50% chance of being a carrier.
Autosomal dominant condition - possible outcomes when one parent has the condition and the other parent is disease free?
The children of these parents have a 2 in 4 (or 50%) chance of having the disease, and 2 in 4 (or 50%) chance of having normal genes.
What is a chromosome disorder?
Chromosome disorders are condition where there is either a structural abnormality, an extra abnormal portion or an abnormal number of chromosomes compared to normal.
Deletion disorders
Deletion disorders occur where a portion of a chromosome is missing.
These syndromes are very rare
One example is cri du chat, which is caused by a missing portion of chromosome 5. Patients have learning, developmental and speech and language difficulties and a characteristic “cat like cry” as infants.
Duplication disorder
Duplication disorders occur where a portion of a chromosome is duplicated.
The chromosome contains twice the number of copies of that gene.
One example is Charcot-Marie-Tooth, which can be caused by a duplication of the short arm of chromosome 17. Patients suffer with sensory and motor neuropathy and have characteristic pes cavus (high arching foot).
What is a translocation disorder?
Translocation disorders occur where a portion of one chromosome is directly swapped with a portion of another chromosome.
The swap can be balanced (reciprocal translocations), where a portion of one chromosome is swapped with a portion of another.
Alternatively they can be unbalanced (nonreciprocal translocations), where a portion of one chromosome leaves the first chromosome and attaches to the other without any exchange taking place.
What do translocation disorders lead to?
Translocation does not usually lead to a specific genetic syndrome, but often predisposes to other conditions such as cancer and infertility. One example is the “Philadelphia chromosome” translocation in acute myeloid leukaemia, which is a reciprocal translocation between chromosome 9 and chromosome 22.
Robertsonian translocations
Robertsonian translocations occur in acrocentric chromosomes. These chromosomes are 13, 14, 15, 21 and 22. They have a longer long arm, which contains most of the genetic material, and a very short short arm with very little genetic information on it. When a person has a Robertsonian translocation, they loose the short arm completely, and the two long arms connect to each other at the centromere, essentially loosing a chromosome when they get rid of the two short arms. In this scenario the person is usually phenotypically normal, but has 45 chromosomes when counted and has a risk of problems in their offspring.
What is Trisomy?
Trisomy is where the person has an extra chromosome.
They have a total of 47 chromosomes.
They have three copies of a particular chromosome.
What is Patau syndrome?
Trisomy 13.
The syndrome varies in severity.
Patients have dysmorphic features, structural abnormalities affecting almost all areas of their body and learning disability. They have characteristic “rocker bottom feet”, where the soles of the feet are convex (rounded outwards) in shape.
What is Edwards syndrome?
This is trisomy 18. The syndrome varies in severity and affects almost all areas of the body, resulting in dysmorphic features and learning disability. They also have “rocker bottom feet”.
What is Mosaicism
Mosaicism is an interesting scenario where the chromosomal abnormality actually happens after conception. The abnormality occurs in a portion of cells in the body and not in others. The person therefore has different genetic material in different cells in their body. Each case is unique and the effects are unpredictable.
“Rocker bottom feet”, where the soles of the feet are convex, is a characteristic feature of what genetic condition?
Patau syndrome, and also Edwards syndrome
Trisomy 13
Patua syndrome
Trisomy 18
Edwards syndrome
Trisomy 21
Down’s syndrome
What is a mitochondrial myopathy?
Abnormal mitochondria lead to poor production of ATP, the molecule that provides energy in the body.
Poor production of ATP leads to myopathy (abnormal muscle function).
They are also responsible for rare forms of deafness, blindness, diabetes mellitus and epilepsy.
What are mitochondria
Mitochondria are organelles that live inside the cell cytoplasm.
The number of mitochondria in a cell varies depending on the function of that cell.
Myocytes (muscle cells) have thousands of mitochondria, whereas adipocytes (fat cells) have very few.
They are responsible for producing ATP for the cell.
Mitochondria contain their own DNA, separate from DNA in the cell the nucleus.
This DNA is arranged in a large circle, unlike the chromosomes found in the nucleus.
Mitochondrial Inheritance
At the time of conception, the sperm carrying the fathers genetic material enters the egg and the DNA in the nucleus of both cells combine.
The vast majority of the mitochondria in that first cell (called the zygote) come from the mother. All of the mitochondria in the sperm are in the tail, which does not enter the egg.
Therefore, the father does not contribute any mitochondria to the zygote and subsequently the fetus and child. Therefore, mitochondrial DNA is primarily from the mother. This is called maternal inheritance.
If we are looking at a specific disease gene in the mitochondria DNA, we need to consider that not all mitochondria within the mothers cells will be affected. The proportion of affected mitochondria that are passed to the offspring will determine whether that individual is affected.
Diagnostic genetic testing
Diagnostic testing involves testing a fetus or a person for a suspected genetic condition. We can test a fetus for a genetic condition via amniocentesis.
An example of this is antenatal testing for Down’s syndrome. Antenatal testing can have implications on the decision to continue the pregnancy.
Where a specific condition is suspected, for example Turner syndrome, it is possible to test directly for that condition in a child or adult.
Predictive genetic testing
Predictive testing involves testing a person for a specific gene mutation that has implications for them in the future.
Examples are the BRCA1 breast cancer gene or the gene for Huntington’s chorea.
Carrier genetic testing
Carrier testing involves testing parents or potential parents for the gene for a specific autosomal recessive condition in order to calculate the risk of passing it to their children. An example of this is testing for the cystic fibrosis gene.
When might genetic testing be undertaken in scenarios outside of diagnostic, predictive and carrier testing?
Genealogical testing
Forensic testing
Paternity testing
What is Karyotyping?
Karyotyping involves looking at the number of chromosomes, their size and basic structure.
In what conditions might karyotyping be helpful in diagnosing?
Down’s syndrome (trisomy 21)
Turner syndrome (45 XO)
What is microarray testing?
Microarray testing involves cutting up the genetic material from an individual using enzymes.
Different genes will have different molecular weights. The chopped up genetic material is then applied to a plate that separates molecules of different weights into different locations.
This can be used to see what genes the person expresses.
Dysmorphic features of downs syndrome?
Hypotonia (reduced muscle tone)
Brachycephaly (small head with a flat back)
Short neck
Short stature
Flattened face and nose
Prominent epicanthic folds (folds of skin covering the medial portion of the eye and eyelid)
Upward sloping palpebral fissures (gaps between the lower and upper eyelid)
Single palmar crease
Features of Kleinfelder syndrome?
Taller height
Wider hips
Gynaecomastia
Weaker muscles
Small testicles
Reduced libido
Shyness
Infertility
Subtle learning difficulties (particularly affecting speech and language)
Features of Turner syndrome
Short stature
Webbed neck
High arching palate
Downward sloping eyes with ptosis
Broad chest with widely spaced nipples
Cubitus valgus
Underdeveloped ovaries with reduced function
Late or incomplete puberty
Most women are infertile
What is cubitus valgus?
Cubitus valgus refers to an abnormal feature of the elbow, associated with Turner syndrome
When the arm is extended downwards with the palms facing forward, the angle of the forearm at the elbow is exaggerated, angled away from the body.
Features of Noonan syndrome?
Short stature
Broad forehead
Downward sloping eyes with ptosis
Hypertelorism (wide space between the eyes)
Prominent nasolabial folds
Low set ears
Webbed neck
Widely spaced nipples
Features of Marfan syndrome?
Tall stature
Long neck
Long limbs
Long fingers (arachnodactyly)
High arch palate
Hypermobility
Pectus carinatum or pectus excavatum
Downward sloping palpable fissures
Features of Prader Willi syndrome?
Constant insatiable hunger that leads to obesity
Poor muscle tone as an infant (hypotonia)
Mild-moderate learning disability
Hypogonadism
Fairer, soft skin that is prone to bruising
Mental health problems, particularly anxiety
Dysmorphic features
Narrow forehead
Almond shaped eyes
Strabismus
Thin upper lip
Downturned mouth
Features of William Syndrome?
Broad forehead
Starburst eyes (a star-like pattern on the iris)
Flattened nasal bridge
Long philtrum
Wide mouth with widely spaced teeth
Small chin
Very sociable trusting personality
Mild learning disability
