Mutations: Human Biology (!!!)

Define the term 'species’

Group of organisms with shared characteristics capable of interbreeding under natural conditions to produce fertile offspring

Define the term ‘population’

Group of interbreeding organisms of the same species living together at a particular time and place

Define the term ‘evolution’

Change in the characteristics of a species over time / number of generations 

Define the term ‘gene pool’

Sum of all alleles carried by members of a population 

What factors influence gene pools?

Mutation and Migration

How does allele frequency change?

• Selective pressure in natural selection (trait is advantageous)

• Chance in genetic drift 

What are the types of mutation?

• Gene mutations

• Chromosome mutations

What are mutations?

Spontaneous mistakes in DNA when DNA molecule is copied during mitosis or meiosis or when chromosomes are separated in meiosis

How do mutations affect an organisms phenotype (characteristics)?

New allele is formed when a DNA molecule is changed by a mutation resulting in a different variation of the trait 

What are the sources of mutations?

• Spontaneous: random error in biological processes (mitosis or meiosis) 

• Induced: mutagens (mutagenic agents) in the environment 

What are some examples of mutagens?

• Chemicals: mustard gas, formaldehyde, sulphur dioxide

• Radiation: ultraviolet light, X rays, cosmic rays

How are mutations inherited?

Mutated DNA is replicated and passed to daughter cells during cellular division (mitosis or meiosis). Mutations can be passed down generations if affected cells are gametes (sperm or ova).

What types of cells are impacted by mutations?

• Somatic: affects body cells (only individual is affected) 

• Germline: affects gametes (individual is generally not affected but mutation is passed to offspring) 

What are point mutations?

Changes in a single nucleotide / change to one nitrogenous base

What are the types of point mutations? (IDIS)

• Inserted

• Deleted

• Inversion

• Substituted

Define inserted point mutations

Inserted: new nucleotide is added to DNA strand (AGT —> ATCG) 

Define substituted point mutations

Substituted: nucleotide is replaced with different base (ATG —> ACG) 

Define deleted point mutations

Deleted: nucleotide is removed from DNA strand (ATG —> AG) 

Define inversion point mutations

Inversion: two nucleotides are switched (ATG —> AGT)

What is a frame shift mutation?

Addition (insertion) or removal (deletion) of a base in a codon alters the reading frame of the gene

What influence does a frameshift mutation have?

Frameshift mutation affects every codon (three bases) beyond the point of mutation and thus changes amino acid sequence and the protein product

What are the effects of point mutations? (MSNN)

• Missense

• Silent

• Neutral

• Nonsense

Define missense as an effect of a point mutation

Missense: changes amino acid and protein product

Define silent as an effect of a point mutation

• Silent: does not change the amino acid and protein product

• Possible as many amino acid are coded by multiple base sequences

Define neutral as an effect of a point mutation

Neutral: changes amino acid with one of the same type (functionally similar) and thus does not change protein structure enough to change protein function 

Define nonsense as an effect of a point mutation

Nonsense: changes the base sequence to STOP codon which stops synthesis of the protein to produce a short protein that may be non functional 

What alleles do gene mutations cause and why?

• Recessive alleles

• Prevent a gene from producing a functional protein 

State types of gene mutations (CAD)

• Albinism

• Cystic Fibrosis

• Duchenne muscular dystrophy

Define the term ‘lethal recessive’

Recessive mutation that is lethal if not masked by normal dominant allele (individual must be homozygous recessive)

What do lethal recessive mutations cause?

• Death of embryo or foetus (miscarriage or spontaneous abortion)

• Early death of child

How is the proportion of lethal recessive alleles impacted?

Proportion of lethal recessive alleles in gene pools is reduced as affected individuals die before reproducing preventing them from passing the mutated alleles to future generations

What are types of lethal recessive alleles?

• Tay-Sachs Disease

• Sickle Cell Anaemia

What is Tay-Sachs Disease?

• Lethal recessive mutation

• Disorder of lipid metabolism inherited in an autosomal recessive pattern

• Missing enzyme results in accumulation of fatty substance in nervous system

• Death occurs in early childhood 

What is Sickle Cell Anaemia?

Change in amino acid which alters the structure of haemoglobin (Hb) in red blood cells creating insoluble fibrous strands 

What type of mutation causes Sickle Cell Anaemia?

Base substitution mutation (single base changed in gene sequence)

What are the symptoms of Sickle Cell Anaemia?

• Haemoglobin cannot transport oxygen effectively causing constant fatigue 

• Sickle cells form clots in capillaries and are destroyed more rapidly then normal cells result in low red blood cell count (anaemia) 

What is Cystic Fibrosis

• Mutation in a gene on chromosome 7

• Gene codes for 1480 amino acids of a protein responsible for regulating passage of chloride ions across cell membranes 

What are the symptoms of Cystic Fibrosis?

• Persistent coughing and wheezing

• Pneumonia and recurring chest infections

• Digestive issues  

What is Duchenne Muscular Dystrophy?

• Gene mutation in mother is inherited by male offspring or mutation in a male zygote

• Wasting of muscles in legs arms, shoulders and chest apparent by ~3-5 years of age 

• Death due to failure of respiratory muscles (~20 - 25 years of age)  

What are chromosomal mutations?

Mutations in all or parts of a chromosome and thus a number of genes 

What are the types of chromosomal mutations? (IDIDN’T)

• Insertion

• Deletion

• Inversion

• Duplication

• Non-disjunction

• Translocation

Define deletion as a chromosomal mutation

Deletion: loss of a section of chromosome and thus loss of numerous genes 

Define insertion as a chromosomal mutation

Insertion: section of a different chromosome is added to new chromosome

Define translocation as a chromosomal mutation

Translocation: section of chromosome breaks off and rejoins the wrong chromosome (non-homologous chromosomes)

Define duplication as a chromosomal mutation

• Duplication: section of chromosome occurs multiple times

• When part of chromatid breaks off and rejoins the wrong chromatid

Define inversion as a chromosomal mutation

• Inversion: breaks occur in chromosome and broken piece rejoins the wrong way around changing order of genes

• Disrupts pairing of homologous chromosomes in meiosis

Define non-disjunction

• Homologous chromosome pair does not separate during cellular division (meiosis)

• One daughter cell has an extra chromosome and other daughter cell has one less chromosome than normal 

What does non-disjunction result in?

Aneuploidy a change in number of chromosomes

What is chromosomal analysis?

• Blood sample, cells from amniotic fluid or cells from placenta

• Information about the karyotype of a foetus

State the types of trisomy

• Partial trisomy

• Trisomy 21 (Downs Syndrome)

• Trisomy 13 (Patau syndrome)

• Trisomy 16

What is trisomy 13 (Patau syndrome)?

• Extra copy of chromosome 13

• 1 in 5000 live births / 80% of affected infants die within a month of birth

What is trisomy 21 (Downs Syndrome)?

Three copies of chromosome 21 instead of two copies (non-disjunction)

What are the symptoms of trisomy 13 (Patau syndrome)?

• Small head

• Cleft palate

• Mental retardation

• Malformed ears and eyes

What is trisomy 16?

• Extra copy of chromosome 16

• Causes spontaneous miscarriage in first 3 months of pregnancy

• Most common form of trisomy affecting more than 1% pregnancies

How does trisomy occur in sex chromosomes and is the result?

• Non-disjunction in first or second meiotic division

• Extra X chromosome (XXY) or extra Y chromosome (XYY)

What is Klinefelter’s syndrome?

• Males with trisomy XXY (Non-disjunction)

• Normal as children but develop Klinefelter’s syndrome as adults (1/650 men)

What are the symptoms of Klinefelter’s syndrome?

• Small testicles that do not produce sperm

• Enlarged breasts

• Sparse body hair

What is Turner’s syndrome?

• Monosomy in sex chromosomes: only one X chromosome (X0)

• Often results in miscarriage, surviving females are short, lack secondary sex characteristics and are infertile 

What is Cri-du-chat syndrome?

• Missing section of chromosome 5

• Deformities in larynx and nervous system result in ‘cat’ like cry

• Intellectual disability, delayed development, small head size, low birth weight and weak muscle tone 

What is monosomy?

Missing all or part (partial monosomy) of a chromosome