Clinical Genetics Flashcards
Why make a genetic diagnosis?
To provide patients with information, genetic counselling, disease prevention, and prenatal diagnosis
What do we need to make a normal human?
The correct number of genes working correctly, in the right gene dosage, with the right gene product in the correct tissues, at the correct time, in a supportive intra-uterine environment.
What is a chromosome?
A chromosome is made of a single molecule of DNA - there are 23 pairs = 46 in total (maternal and paternal). Each chromosome has hundreds of genes.
What is a gene?
A specific stretch of DNA where the sequence contains genetic instructions. They code for functional proteins.
How are genes arranged & what can be found between genes?
Genes are arranged one after the other along the DNA of a chromosome, with stretches of non-coding DNA between them, which is important for regulation.
How many protein-coding genes do humans have?
Humans have about 23,000 genes that code for proteins.
What are nuclear genomic sequences?
They are particular sequences of DNA that allow proteins to switch a gene on or off, produce RNA, influence activity of other genes, and affect the folding and packaging of DNA.
What does human DNA code for?
In the translation of mRNA (tRNA and rRNA), enabling modification of other RNA molecules (snRNA), inhibition of translation and repressing synthesis of target genes (miRNA), and regulatory roles (tiny/long RNA).
What are the 2 types of cell division?
Mitosis is normal cell division in which identical daughter cells are formed. Meiosis is specialised cell division responsible for the formation of gametes.
What is the function of meiosis?
Reduction division - 23 chromosomes per gamete, and re-assortment of genes – independent segregation of chromosomes and chromatids as well as crossing-over to promote genetic diversity.
Describe the mechanism of meiosis.
Each homologue replicates to give two chromatids, homologues pair, exchange of material between non-sister chromatids (crossing-over, recombination), and end with 4 haploid gametes.
How could errors in DNA replication and meiotic cell division cause harm?
DNA replication can lead to new mutations (copying errors), and meiotic division can cause anomalies of chromosome number and structure.
How can the genome be examined and why?
Can be done in clinical practice using techniques like sequencing, microarray analysis, fluorescence in situ hybridisation, and light microscopy to highlight variants in the genome.
How do we identify if a pregnancy is at increased risk of a genetic condition?
Through genetic diagnosis in a relative, patterns of affected people in the family, results of screening or scans in the pregnancy, and results of genetic testing in a pregnancy.
Give an example of some pathogenic changes in the genome.
Pathogenic changes include nonsense mutations and frameshift mutations in coding DNA which are likely to disrupt gene function.
Other than pathological effects, what are other clinical effects of genomic variations?
No effect, normal variation, increasing susceptibility towards a condition, and directly causing a condition.
What are the main classes of genetic disorders?
Mutations in single genes, common complex/multifactorial diseases, copy number variants, chromosome imbalance, and mitochondrial disorders.
What are single gene disorders and where can they occur?
Pathological mutations associated with genes can occur in the coding sequence of a gene (exon), non-coding sequences necessary for correct gene expression (intron), and regulatory sequences.
Are single gene disorders harmful?
Variants may not necessarily be harmful.
What are the types of mutations affecting the gene sequence?
Missense mutations, non-sense mutations, and frameshift mutations.
Are missense mutations always harmful? Why?
Missense mutations are not always harmful due to the degenerate nature of coding and the possibility of replacement by a chemically similar amino acid which will not alter protein function.
Which mutations are most likely to cause damage?
Non-sense and frameshift mutations are more likely to cause damage as they affect multiple codons.
When is a gene mutation pathogenic?
When it affects the function of the protein, either distorting its function or resulting in none being made at all.
