Lecture 16 - How are we all different?

Question 1

Genetic variation

Answer 1

Differences among individuals in the composition of their genes or other DNA segments

Question 2

Mendel’s laws of inheritance

Answer 2

law of segregation, law of independent assortment, law of dominance

Question 3

Law of segregation

Answer 3

When gametes form, alleles are separated so that each gamete carries only one allele for each gene i.e. 50% chance of receiving one allele from mum (same from dad)

Question 4

Law of independent assortment

Answer 4

The segregation of alleles for one gene occurs independently to that of any other gene - this is possible through recombination at meiosis

The exception to this law is when two genes are close together on a chromosome - genetic linkage (usually are inherited together). This is because there is less chance of a cross over between them these are often referred to as genetic linkage

Question 5

Law of dominance

Answer 5

Some alleles are dominant while others are recessive; an organism with at least one dominant allele will display the effect of the dominant allele

Recessive allele = version of the gene that does not encode a functional protein
Heterozygous = should be enough protein provided from the dominant allele (which encodes the functional protein)
Homozygous recessive = no functional protein produced in a metabolic pathway can get a build up of intermediates

Question 6

Allele

Answer 6

An allele is an alternative form of a gene (one member of a pair) that is located at the same place on a chromosome

One from mum and one from dad

Question 7

Homologous chromosomes

Answer 7

Homologous chromosomes are made up of chromosome pairs of approximately the same length, centromere position, and staining pattern, for genes with the same corresponding loci. One homologous chromosome is inherited from the organism’s mother; the other is inherited from the organism’s father.

Question 8

Sister chromatids

Answer 8

A sister chromatid refers to the identical copies (chromatids) formed by the DNA replication of a chromosome, with both copies joined together by a common centromere

Question 9

Recombination

Answer 9

Recombination is a process by which pieces of DNA are broken and recombined to produce new combinations of alleles.

Question 10

Genetic linkage

Answer 10

when two genes are close together on a chromosome

Question 11

Exception to independent assortment law

Answer 11

Genetic linkage

Question 12

Heterozygous recessive mutation (Aa) vs homozygous recessive mutation (aa)

Answer 12

Heterozygous - lost one copy from one parent, but other can keep the process going/the other is function
Homozygous - Accumulation of protein/product at the point where the mutation is to a certain protein therefore there is no final product, dysfunctional from both parents therefore show the dysfunctional phenotype

Question 13

Why are we all different?

Answer 13

We inherit a unique combination of alleles from our parents. 
The DNA of any two people is about 99.4% identical. 
So it differs at about 20 million places (0.6% of the total of 3.2 billion base pairs). 
5% of these differences (1 million differences) might affect how our genes function.
Environment determines how some of these genetic differences affect us

Question 14

Phenylalanine breakdown

Answer 14

If the different genes for the different proteins in the line up are mutated and no longer produce active enzyme then there is a buildup caused and not enough products produced.

For example mutation in the first gene - no enzyme one is produced therefore no enzyme to convert initial substrate to the next product etc. so too many initial substrates which could interact with other enzymes and cause unwanted effects also too little of other intermediates

Defect in the first enzyme leads to the accumulation of phenyl amine and to PKU. Leads it to be nonfunctional so it decreases the amount of tyrosine produced and therefore the rest of the metabolic pathway chain is affected.

PKU can lead to intellectual disability, seizures, behavioural problems and mental disorders

Question 15

Alkaptonuria

Answer 15

Alkaptonuria is an autosomal recessive genetic disorder where the enzyme homogentisate 1,2-dioxygenase is not produced (involved in the ring cleavage step)
One of the first examples where mendelian genetics could be applied to humans
Showed that in born errors of metabolism could be inherited
Leads to black urine (and sometimes darker colouring of bone/cartilage)
Generally does not cause major health concerns

Question 16

Phenotype can be affected by genotype and by your environment (in terms of phenylalanine)

Answer 16

Environment - A low phenylalanine diet prevents intellectual disability and associated problems in PKU individuals. ELiminate detrimental consequences by changing your diet

Genetics - Phenylalanine is transported across the blood-brain barrier. Genetic variation means the efficiency of this transporter differs between individuals. Individuals with less efficient transporters have lower levels of The in the brain and less damage (higher IQ)

Question 17

What is the link between genotype and phenotype?

Answer 17

The genotype of an organism is defined as the sum of all its genes. The phenotype of an organism is the observable physical or biochemical characteristics of an organism, determined by both genetic make-up and environmental influences.

Question 18

PKU (phenylketonuria)

Answer 18

a condition that makes it impossible for babies to metabolize certain proteins. autosomal recessive disease.

An autosomal recessive genetic disorder where the enzyme phenylalanine hydroxyls is not synthesised - this means we do not get the conversion of Phe to Tyr
Build up of Phe —> can go through other pathways to form toxic metabolites
Less Tyr produced —> Tyr is used to form neurotransmitters, so less of these are made
THis can lead to intellectual disability, seizures, behavioural problems, and mental disorders

Question 19

Mutation causing PKU

Answer 19

R408W mutation in phenylalanine hydroxyls (PAH) gene
Codon 408 for arginine is mutated into a codon for tryptophan
Specifically, A (AGG) —> U (UGG) in mRNA
AGG encodes arginine
UGG (TGG in table) encodes tryptophan
Change in AA occurs in the region that is necessary for the protein to fold correctly
Normal = tetramer
Mutation = incorrectly folded protein forms an aggregate that the cell degrades —> no active PAH protein