Genetic disorders Flashcards
Define allele
Variant form of a gene in the same locus
Humans are diploid because they have two alleles at each genetic locus
Define genotype
Pair of alleles represents a genotype of a specific genes
Broadly, the genotype refers to the genetic makeup of an organism
Define homozygous
A genotype that features two identical alleles
Define heterozygous
A genotype that features two different alleles
Define phenotype
Composite of an organism’s observable characteristics or traits
Results from the expression or the interaction between an organism’s genotype and environmental factors
Define dominant
Allele that will be manifested in the phenotype of a heterozygote
Define recessive
Allele that won’t be manifested in the phenotype of a heterozygote, manigestation only results in homozygous individuals
Define mutation
Permanent alteration of the nucleotide sequence in the genome
Define wild type
An allele which is not mutated and codes the phenotype most common in a natural population
Define SNP
Mutation carried by more that 1% of the population
Leads to variations in the amino acid sequence
Also occur in noncoding regions of DNA
If SNPs occur in a gene, the gene is described to have more than one allele
Does not significantly affect the phenotype, so is not selected for and therefore survives in the population
Define mendelian disorder
Disorder controlled by a single locus in an inheritance pattern based on Mendel’s Law
Define genetic susceptibility
Increased likelihood of developing a particular disease based on a person’s genetic makeup
What information does DNA provide?
Information to understand how living organisms function
Study and treat disorders
Understand disease susceptibility
Study history and evolution
Make drugs
Understand and treat cancer
What is a genetic disorder caused by?
One or more abnormalities in the genome
TRUE or FALSE
All mutations are passed down
FALSE
Only if it occurs in the germline
Example of an autosomal dominant condition
Huntington’s
Example of an autosomal receissive condition
Cystic fibrosis
Example of a X-linked disorder
Haemophilia A
Example of a non disjunction condition
Trisomy 21
Example of a condition caused by DNA deletion
Cri-du-chat
What are the 4 types of genetic disorders?
Single gene
Chromosomal
Multifactorial
Somatic
Types of chromosomal genetic disorders
Deletion
Duplication
Inversion
Translocation
Non disjunction
Types of single gene genetic disorders
Autosomal dominant
Autosomal recessive
X-linked
Pedigree of autosomal dominant conditions
Occurs in half of the offspring
Pedigree of X-linked recessive
Men are affected
Women are carriers
For women to be affected, the mother must have both copies of the recessive allele
Pedigree of a Y-linked dominant
Never occur in females
Occur in all male descendent of an affected male
Pedigree of X-linked dominant
If mother have the disorder
Males and females have even chance of receiving conditions
If father has the disorder
Daughters will 100% get disorder
None of the sons have disorder
If both have the disorder
- 100% of daughters will have disorder
- 50% of sons will have disorder
What is congenital afibrinogenemia?
Condition characterised by the lack of fibrinogen protein in the plasma
Leads to increase in coagulation times
What is fibrinogen?
Plasma hexameric glycoprotein
Which cells secrete fibrinogen?
Secreted mainly by hepatic parenchymal cells
What is the role of fibrinogen?
Plays an important role in haemostatic balance and support for platelet aggregation
What mutation leads to congenital afibrinogenemia?
Mutation to one of the 3 fibrinogen genes
FGA
FGB
FGG
Describe the process behind polymerase chain reactions
Technique used to make copies of a specific DNA region in vitro
Goal = make enough target DNA region so that it can be used
How is Tag polymerase specialised for PCR?
Isolated from Thermus aquaticus bacteria
It is very heat-stable
Most active around 70C
What is required for Taq polymerase to carry out its function?
Primer
What are primers?
Specific sequences of DNA
Bind via complementary base pairing
What is gel electrophoresis?
Technique used to visualise PCR reactions
Fragments of DNA are pulled through a gel matrix by an electric current which separates DNA fragments according to size
Exploits the negative charge of DNA
DNA fragments of the same length form a band on the gel which can be stained with a DNA-binding dye
Describe the process behind Sanger sequencing
- The DNA molecule is denatured
- The solution with a single stranded DNA is added to DNA primers, DNA polymerase, four type of dNTPs and ddNTPs
- ddNTPs bind (lack hydroxyl groups) and elongation is terminated
- So if a ddNTP binds to the first complementary codon on a strand = reveals the first codon of the DNA
How do ddNTPs terminate sequence elongation?
Lack hydroxyl groups
Nucleotides without hydroxyl groups cannot create phosphodiester bonds with adjacent nucleotides
How do ddNTPs tell which base it is bound to?
Colour coded
What are types of point mutations?
Silent
Nonsense
Missense
What are conservative point mutations?
Mutated protein’s function is not too different from that of the wildtype
Causes limited phenotypic expression
What are non-conservative point mutations?
Do have a big effect on wild type since the protein expressed as a cause of the point mutation is very different from that of the wild type
Mechanisms underlying point mutations
Substitution
Insertion
Deletion
Inversion
Describe the nomenclature for describing point mutations
g.1749T>G
Gene 1749 T is replaced by G
On amino acid 45 cysteine is replaced by phenylalanine
