Lecture 11 - Genetic Methods Flashcards
What is genetics research?
- Relatively new field of research – mid-19th century onwards
- Considered to be the study of heredity i.e. the study of how traits are passed from generation to generation
Heredity
The passing of physical and mental characteristics from one generation to another
Genotype
The underlying genetic makeup of a biological organism
Phenotype
The observable characteristics of a biological organism. These may be physical or behavioral
Dominant allele
An allele that is expressed in the phenotype, even when only one copy is present
Recessive allele
An allele that is only expressed when two copies are present in the genotype
How has genetics research changed from the 1850s to now?
- We now have the ability to look a little closer than Mendel
- Deoxyribonucleic acid (DNA) can be found in the nucleus of every cell of an organism
- It is composed of two chains of nucleotides that coil around each other to form a double helix
- Bases consist of four unique compounds: Adenine, Guanine, Cytosine, Thymine. These are always matched A to T and C to G
- This double helix contains the genetic instructions for the development, functioning, growth and reproduction of all known biological organisms. This means that the entire DNA of a being can be found in each individual cell
- These strands are “unzipped” and read by ribonucleic acid (RNA) molecules to produce protein strands; this process is called translation
- (It’s like RNA reads DNA to 3D print)
DNA to chromosomes
- When in a cell’s nucleus, these long strands of DNA are called chromatids and are usually tangled together when a cell is active
- When a cell needs to divide (mitosis), chromatids undergo condensation - the act of coiling tight like a spring to form a chromosome
- Each individual chromatid is about 6ft long if stretched out
- Typical humans have 46 chromosomes (23 pairs). All pairs are XX, aside from the final pair which may vary. This pair codes for biological sex, with biological females having XX and males having XY
- Individual sequences of DNA on these chromosomes are called genes, with humans possessing between 20,000 to 25,000 genes. The aggregate of these genes is called a genome
- Some phenotype traits may be programmed by a single gene (pleiotropic), while others may be influenced by a combination of genes (polygenic)
- For example, in humans, the gene that codes for ear wax is on chromosome 16 (locus). This gene has two versions (alleles); a dominant version for wet ear wax and a recessive version for dry ear wax
Dr Paula Morgan’s genetics TL; DR
- DNA = Letters
- Genes (alleles) = Words
- Chromosomes = Books
- Genome = Library
- The information on these chromosomes are the biological programming behind life as we know it
Why bother studying genetics?
- By understanding genes on a functional level, we’re able to open avenues of greater understanding of biology
- Understanding and decoding the human genome has been the sole purpose of the Human Genome Project for the last 50+ years (costs $3 billion)
- By understanding the base causes for many traits, we can further target medicine, treatments and quality of life improvements e.g. discovery of breast cancer gene
- Fundamentally, the study of genetics is the study of the building blocks of life
- This includes combating many genetic disorders such as Huntington’s, Downs Syndrome and Fragile X syndrome
Who was Gregor Mendel?
- Gregor Mendel, credited as the first geneticist (1822 – 1884)
- Austrian monk and botanist
- Spent a lot of time breeding and cross breeding peas
- Wasn’t recognised for his genetics work within his lifetime
- As part of his findings, he noted that peas get one version of each trait from each parent (allele), some seemed to be dominant (very likely to be shown in finished organism) while others were recessive (less likely to be shown in finished organism)
- Dominant traits are easily expressed in an organism’s phenotype
- On the other hand, recessive traits are only expressed in the absence of an overshadowing dominant trait
- We now know this is due to the pea’s genotype - it’s genes
What is Mendelian inheritance?
- Many of your phenotype traits will depend on your parents, as you receive an allele of each gene from each
- Example: cheek dimples
- Dimples are dominant
- Assuming both parents have a dominant and recessive allele, the proportion of dimpled to non-dimpled offspring will be 3:1 (two parents with dimples can have a child with no dimples)
- An ‘allele’ is basically a ‘version’ of a trait. Many versions of that trait may exist e.g. hair color (one version of each trait from each parent)
What are the two fundamental rules of Mendelian inheritance?
- (1) Segregation = traits are either dominant or recessive
- (2) Independence = varieties of each trait sort independently of each other
What are x-linked conditions?
- Some things don’t quite follow Mendel’s laws
- X-linked conditions: some recessive traits are more prevalently expressed in males when compared to females. This is because they may not have a dominant allele on their (much shorter) Y chromosome. However, this isn’t always true
What are some examples of x-related conditions?
- Colorblindness: first reported case of human X linkage
- Turner Syndrome (effects females; X partially missing). Effects 1/2,500
- Klinefelter Syndrome (effects males; X (+) XY). Effects 1/750
- Fragile X Syndrome (repeat on gene for FMR1 protein – FMR1 is necessary for brain development so the longer the repeat, the more severe the symptoms). 1/2:4000 males, 1/6000 females
What is Triple X syndrome (XXX)?
Individuals with three X chromosomes, typically assigned female at birth. Most have no severe physical differences but may have a slightly taller height and an increased risk of mild developmental and learning challenges
What is Jacob’s syndrome (XYY)?
Individuals with this condition have an extra Y chromosome, typically assigned male at birth. They may be taller than average and have a slightly higher chance of learning difficulties, but they usually have normal sexual development and fertility
What are some commonalities amongst x-linked conditions?
- All x-linked conditions are generally associated with distinct physical features, learning disabilities, social and behavioural difficulties, language delays and emotional issues (not all individuals with these syndromes will exhibit all of these symptoms, and the severity and presentation can vary widely from person to person. Additionally, each syndrome has its own unique set of characteristics and associated health concerns)
What are sporadic mutations?
- Caused by errors or interference in typical cell division. These mutations can happen naturally or be the result of environmental factors (e.g., radiation)
- Often includes errors in chromosomal numbers
What is Down’s syndrome?
Effects 1/1000
- Majority of cases due to trisomy (extra version) of chromosome 21(not passed down)
- Some symptoms (e.g., facial dysmorphology) evident from birth, while others (e.g., short stature, potential learning difficulties) may only become apparent later in life
What is William’s syndrome?
Effects 1/18,000
- Due to microdeletion on chromosome 7 (approx. 25 genes)
- Some symptoms (e.g., facial dysmorphology) evident from birth, while others (e.g., potential learning difficulties) may only become apparent later in life
What are polygenic traits?
- These conditions/disorders rely on coding from multiple genes and may not consistently follow Mendelian rules
- Schizophrenia effects 20m worldwide
- Individuals are considered to be genetically predisposed to develop SZ, suggesting a clear genetic basis (but some interaction with the environment)
What are twin studies?
- Compare monozygotic (genetically identical) and dizygotic twins – study people who live with the same parents and are identical or not
- Peter B. Neubauer (three identical strangers)
- Sealed until 60s
- Not very ethical, but very academically interesting for genetic research
What are genomic studies?
- Inspect the genome of specific groups
- Identify allele commonalities
- E.g. studying an extended family prone to Huntington’s helped identify the genetic markers (1 dominant allele)
- Huntington’s symptoms include loss of motor control, cognitive decline, and psychiatric disorders
