Genetics and Genomics Flashcards
Differentiate between genetics and genomics and assess key historical events in their development Understand the relationship between genotype and phenotype and forward and reverse genetics Differentiate the terms "genome", "transcriptome", and "proteome" Appreciate the influence of environment and epigenetics on phenotype Differentiate acquired vs inherited and sample vs complex genetic diseases
Define the terms “genetics” and “genomics”.
Genetics is the study of genes and their inheritance. Genomics is the study of the genome - the complete set of genetic information (including non coding DNA etc etc.)
Describe the organisation of genes
They are located on chromosomes - long pieces of DNA which are inherited during reproduction. 1 small chromosome in the mitochondria - rest in nucleus. Genes have associated promoters that ensure they are transcribed into RNA. Exons are interrupted by introns which are spliced out after transcription. Some genes are transcribed into non protein-coding RNA.
Define “gene”
A sequence of nucleotides, the order of which that determines the order of monomers in a protein or nucleic acid. They are the units of heredity.
How do somatic cells and gametes differ in terms of their genetic material?
Somatic cells have 23 pairs of chromosomes, 22 autosomal and 1 sex pair. Gametes have half the amount, and are called haploid cells while somatic cells are diploid.
Describe the genome
Each set of 23 chromosomes contains about 3billion nucleotides. The whole genome has about 20,000 protein coding genes. This is 25% of 6 billion nucleotides (both sets of 23). Removing introns, this reduces down to about 2% of nucleotides. The rest is regulatory regions, introns, non protein coding, repetitive and non repetitive DNA. Most of this has no known function.
Define and explain the term “transcriptome”
The transcriptome refers to all of the RNA in a cell/cell type. Some definitions include only protein coding RNA, some include non-protein coding RNA. The transcriptome is highly variable in each cell type, and not all proteins are expressed in all cell types. The transcriptome can even change in a single cell, depending on the conditions/time.
Define and explain the term “exome”
The exome refers to all of the exons in the genome. This is just the genome, with the introns removed. It does not change from cell to cell.
Define and explain the term “proteome”
The proteome refers to the complete set of proteins expressed in a particular cell type at a particular time. For this reason, the proteome is also variable depending on time/conditions.
Define “genotype” and “phenotype” and explain the link with forward and reverse genetics.
The genotype of an organism is the genetic constitution of an organism, overall or at specific loci.
The phenotype of an organism is the physical/biochemical appearance of an organism.
Forward genetics is the process of looking at phenotype to determine genotype, allowing us to hone in on the gene underlying a certain characteristic (mendels peas)
Reverse genetics is manipulating the genotype and observing the phenotype, allowing us to understand the function of a gene.
Describe molecular genetics and its link to human disease
SCD was one of the first inherited diseases to be defined in molecular terms - meaning that it was defined in terms of a molecule causing the disease. (As opposed to virus/bacteria). In terms of SCD, a mutant haemoglobin molecule causes the disease.
Describe and explain Sickle Cell Disease in terms of its underlying genetics.
A mutation in the Hb molecule (forming Hb-S) causes the Hb to aggregate, forming sickle shaped RBCs and leading to painful episodes, frequent infections, and anaemia. Peptide sequencing detected the mutation in Hb to be an AA change from Glu —> Val in the B globin protein. Later nucleotide sequencing confirmed this.
Describe and explain Sickle Cell Trait
Sickle Cell Trait is the phenotype often displayed by carriers of SCD. SCD carriers are not completely asymptomatic, which is due to the small amounts of sickle rbcs causing symptoms. Also due to the ability of HbA to inhibit aggregation by interaction with HbS. Patients with sickle cell trait have increased resistance to malaria, meaning the HbS allele is common in malaria prone regions.
Describe and explain what is meant by a monogenic disease.
A monogenic (aka mendelian - follows mendelian ratios) disease is a disease caused by a mutation in a single gene. SCD and cystic fibrosis are common monogenic diseases, Werner’s syndrome (premature ageing) and permanent neonatal diabetes are very rare. Analysing the family history can tell us more about the disease.
List the 5 classes of monogenic disease and briefly explain what is meant by them
Autosomal recessive - A recessive disease carried on an autosome. Disease can skip generations, parents of affected must both be carriers.
Autosomal dominant - Dominant allele carried on an autosome. Cannot skip generations, every affected person has an affected parent.
X linked recessive - A recessive allele carried on the X chromosome. Mostly males affected due to needing only one copy of the allele for the phenotype to be expressed.
X linked dominant - Females more often affected than males, can be both.
Mitochondrial - Only passed on by females but can affect both males and females.
Describe what is meant by a polygenic disease
A polygenic disease refers to a disease which is caused by mutations in a variety of different genes - most diseases are like this, including heart disease, diabetes, obesity. In order to identify the genomic regions involved in polygenic diseases, whole genome analysis is required.
