Introduction to Genes and inheritance

Question 1

DNA

what is the building block of DNA?
what makes this up? (3)
different bases?

Answer 1

DNA = Deoxyribonucleic Acid

The building block of DNA is nucleotides, a nucleotide is made from a pentose sugar, a phosphate group and an nitrogenous base (thymine, adenine, cytosine, guanine)

Question 2

Nucleotide base pairing

how many H bonds?

Answer 2

Adenine only pairs with thymine (2H)

Guanine only pairs with cytosine (3H)

Question 3

pyramidine and purines

Answer 3

Ys are pyramidines so thymine and cytosine

adenine and guanine are purines

Question 4

DNA is a double helix. How? bonding?

Answer 4

The DNA is a double helix, the sugar-phosphate backbone is joined by very strong bonds between the phosphates, while the weak hydrogen bonds between bases can be broken and unzip, to be transcribed.

The phosphate-deoxyribose backbone is on the outside while the bases hydrogen bond in the middle

Question 5

what is a gene?

occupy what?
passed on from?
what do they encode?
how many copies of gene?

Answer 5

Within the DNA there are sections/sequences of nucleotides called genes.
They occupy fixed positions.
They are passed on from parents to offspring.
Genes contain the instructions for making proteins

We always have 2 copies of each gene

Question 6

From DNA to protein - short summary

4 step process?

Answer 6

1. DNA zip open and a pre-mRNA strand is created.
2. Introns are then spliced out.
3. mRNA leaves nucleus and gets translated into an amino acid chain.
4. This polypeptide chain then folds up into the final molecule / protein.

Question 7

What is a chromosome?

what is it made from? joined by?

Answer 7

A chromosome is an organized way of packaging and storing DNA in the nucleus of the cell.

This chromosome is made from two chromatids, joined by a centromere. There is a long arm and short arm.

Question 8

Chromosome number

how many pairs in humans?
how many autosomes? sex chromosomes?

Answer 8

Different organisms have different numbers of chromosomes.

There are 23 pairs of chromosomes in the human genome, 23 chromatids from the father and 23 from the mother, this forms the entire 46 chromosomes.

Chromosomes 1-22 are the autosomes, while X/Y are the sex chromosomes. All the chromosomes make up the genome.

Question 9

Genome

Answer 9

The genome is an organism’s entire set of DNA

and includes all of its genes

Question 10

2 different defects in the genome (types_

Answer 10

Single gene defects and chromosome abnormality

Question 11

chromosomal aberrations (2 types)

Answer 11

Defects in the genome at “macro” level

Can be either numerical or structural

Question 12

Numerical change chromosomal aberrations
examples

2 examples

Answer 12

A numerical change is when there is a numerical difference in the number of chromosomes, for example downs syndrome (trisomy 21), where there is an extra copy of chromosome 21.

Monosomy X (Turners Syndrome) is the absence of the Y sex chromosome.

Question 13

Structural change chromosomal aberrations

5 different structural chnager abberations?

Answer 13

You can have translocation with chromosomes, which is when a part of a gene breaks off and then swaps with another one on a different chromosome. Depending on where this break is, this would determine the disease.

These structural abnormalities can be seen in karyotypes also, by oddly shaped chromosomes, which would indicate that there has been some breaking off and swapping of parts of chromosomes.

Other examples of structural abnormalities include:

Deletion: A chunk (gene) of a chromosome is deleted
Duplication: A gene in the chromosome is repeated (i.e. doubled)
Inversion: Where the gene gets switched round in reading frame
Substitution: Gene on one chromosome is substituted for another

Question 14

Summary of chromosomal defects

caused by?

numeriacal aberattions? 2 examples

structural aberations? examples>

dectectable how?

Answer 14

These are usually caused by a failure during cell division (meiosis).

Numerical aberrations lead to missing (monosomy – Turner Syndrome) or extra chromosomes (triosomy – Down Syndrome).

Structural aberrations lead to missing a part or gaining an extra part, or a part has switched place (with another part). (Cri du chat syndrome = 5p deletion, 22q11.2 deletion syndrome, Charcot-Marie-Tooth disease Type I = 17p12 duplication).

This ultimately leads to having too much or too little or mixed up chromosomal (genetic) material.
These alterations in chromosome number or structure can be pathological and cause birth defects.

Usually detectable through the microscope doing karyotyping.

Question 15

Single gene defects

defetcs in micro level called?

Answer 15

Defects in the genome at a microlevel are called point mutations

This can occur from just one nucleotide changing in a gene and it can result in disease.

Question 16

point mutations - 4 types?

Answer 16

Wild type
silent mutation
missense mutation
nonsense mutation

Question 17

missense mutation

effect?

Answer 17

If ATG was mutated to GTG, this would cause CAC -> Histidine. So this is a completely different amino acid and if the properties are different, it will lead to different folding of the protein and so can alter the function.

Question 18

missense mutation
Example of disease:

codon from what to what? amino acid from what to what?

net result of this?

Answer 18

Example of disease:
Sickle-cell anemia
Codon change due to missense mutation: GAG to GTG in the haemoglobin gene.
Amino acid change from Glutamic acid to Valine.
Red blood cells with normal haemoglobin are smooth and round and glide easily through blood vessels.
Red blood cells with defect haemoglobin are misshapen (sickle-shaped) and are rigid and sticky.

Question 19

Nonsense

effect?

Answer 19

There could be mutation to ATC -> UAG -> STOP. As it codes for a stop protein the synthesis will stop

Question 20

wild type

effect?

Answer 20

The wild type of the protein is the normal protein, this is coded for by a normal gene and hence mRNA codon

Question 21

silent mutation

effect?

Answer 21

Say there was a mutation in the gene and the nucleotide G was swapped for an A. Giving ATA, this would cause: ATA -> UAU -> Tyrosine.

This is known as a silent mutation as there is no effect; this is because one amino acid will be coded for by multiple codons.

Question 22

(indels) - what are they?

Answer 22

Another defect in the genome at a microlevel are insertions/deletions (indels)

Question 23

Insertion and deletions effect

what does it causes?
leads to what disorder?

Answer 23

This is where nucleotides are added in or removed from the DNA sequence. These insertions or deletions cause a shift in the reading frame (frameshift varients) can lead to Mendelian single gene disorders.

This can cause truncated proteins that don’t function properly.

Question 24

Summary of single gene defects

when can mutation occur? (2)

Answer 24

When a genetic defect is only affecting one gene, we refer to this as a single gene disorder.

The defect is a result of a single mutation that appear at nucleotide level; sometimes just affecting one single nucleotide.

The mutation responsible can occur spontaneously before embryonic development (e.g. in meiosis) or it can be inherited from one or two parents.

Sometime these alterations of the DNA code can be pathological and cause disease.

However, genetic disorders are rare in themselves.
Usually detectable through DNA sequencing.

Question 25

Defects in the genome can cause disease

single gene vs chromosomal

Answer 25

Single gene defects
An individual can have normal chromosomes in number and structure, but still have a disease caused by a mutation in one of the genes on one of the chromosomes.

vs chromosome abnormality
Similarly, a personal can have normal genes, however, if the number or structure of chromosomes are abnormal, then that can affect the genes to not work properly, and thereby cause disease.

Question 26

Single gene disorders often have a predictable inheritance pattern

5 types?

Answer 26

There are several types of single gene disorders that can be inherited

Autosomal dominant     (mutated gene on autosomes)
Autosomal recessive                 

X-linked dominant (mutated gene on X chromosome)
X-linked recessive

Y-linked (mutated gene on Y chromosome)

Question 27

Cystic Fibrosis is an autosomal recessive disease

heterozygous?
homozygous recessive?

Answer 27

An unaffected person can carry the deletion in one of their gene copies.

If an individual has two defective gene copies, then they will develop the disease.

Question 28

Monogenic Autosomal Recessive

Answer 28

The child receives an allele from the father and mother, the allele can be normal or mutated. If an individual has one normal allele and one mutated recessive allele, they are a carrier of the disorder.

Two recessive alleles are needed for the disorder to be seen in the phenotype

Males and females are equally affected.
Typically often no family history.

Question 29

Autosomal recessive disorders

Examples (6)

Answer 29

Cystic Fibrosis
Sickle cell anaemia
Spinal Muscular Atrophy
Phenylketonuria (PKU)
Tay-Sachs disease
Meckel-Gruber Syndrome

Question 30

Autosomal Dominant

how many faulty genes?
parents needed to have it?

chance of passing trait?

Answer 30

one faulty gene copy is enough to cause disease in an autosomal dominant inherited condition

Only one parent needs to carry the mutated allele.

An autosomal dominant trait is expressed in heterozygotes (dD).
Usually the mutant homozygotes are lethal (DD).
So an alteration in only one gene is sufficient to cause the disorder.
Males are equally affected as females
An affected heterozygote has a 1 in 2 chance of passing the trait on to his or her offspring.

Question 31

Autosomal Dominant disorders

Examples (6)

Answer 31

Achondroplasia
Huntingtons
Marfan syndrome
Polycystic Kidney Disease
Polydactyly
Familial hypercholesterolaemia

Question 32

X-linked recessive

faulty gene located where?
expressed in? carried by?

son of female carrier has how much chance?
daughter of female carrier, chance of being a carrier?

Answer 32

In X-linked conditions the faulty gene copy is located on Chromosome X.

X-linked recessive traits are expressed in male hemizygotes and carried by a female heterozygote.
The son of a female heterozygote has a 1 in 2 chance of being affected.

The daughter of a female heterozygote has a 1 in 2 chance of being a carrier.

When an affected male has children all his daughters will be carriers and none of his sons will be affected.

It is important to remember that X-linked conditions
cannot be passed on from father to son!

Question 33

X-linked recessive

Can you work out why there is no transmission of disease from father to son?

Answer 33

Affected fathers cannot pass on the disease to a son, because any son would get a Y-chromosome from their father.

Question 34

X-linked recessive – most common situation

3 key features?

Answer 34

This is how X-linked recessive most commonly presents:

• Only males are affected
• The females are carriers
• There is no male to male transmission

Question 35

X-linked recessive – the more rare situation of an affected father having children with a carrier mother

chance of both parents passing on gene?

Answer 35

Same situation as with autosomal recessive inheritance, i.e. 1:4 chance both parents pass on their faulty chromosome X.

The affected daughter will develop the disease as her affected brother.

Question 36

Examples of X-linked recessive disorders

4 examples?

Answer 36

Red-Green colour blindness
This occurs in 8% of males and 0.4% of females.

Duchenne Becker muscular dystrophy (DBMD)
occurs in approximately 1 in 3,500 male births, and in about 1 in 50,000,000 female births.

Haemophilia A and B
Hemophilia affects males much more frequently (1 in 10,000) than females (1 in 100,000,000).

X-linked ichthyosis
Could not find any prevalence figures for female, but it is 1 in 10,000 for males.

Question 37

X-linked dominant

affacetd fathers? 2 key features

how is a male affected?

chance of affected mother passing on gene to son and daughter?

Answer 37

As with autosomal dominant disease, in X-linked dominant disease you only need one faulty gene copy to be affected.
Therefore, women as well as men can be affected.

However, affected fathers still do not pass on the condition to their sons, but all their daugthers will be affected.

If a male is affected, it is because he has inherited the faulty gene copy from his mother.

An affected mother has a 50% chance of passing on the faulty gene to both sons and daughters.

Question 38

Examples of X-linked dominant disorders

Answer 38

Cranio-fronto-nasal dysplasia
Hypophosphataemic Rickets (males usually have a more severe phenotype than females)

Question 39

X-linked dominant (XLD)
on a pedigree

average affected with affected female?
affected father?

Answer 39

For any of these X-linked dominant disorders, if you draw out a pedigree after taking a family history, you can see how the condition is expressed in males and females.

With an affected female, on average half her sons and half her daughters will be affected.

An affected male will transmit XLD trait to all his daughters but NONE of his sons.

Remember, father to son excludes any X-Linked inheritance!!

Question 40

X-linked dominant / male lethal

if no men or less men than female? meaning?

Answer 40

Sometimes the condition is so bad that if you do not have a normal Chromosome X, it would be fatal.

In this pedigree is it indicated that there were pregnancies that never survived to term and one could speculate that those were males.

This is not an uncommon pattern in X-linked dominant diseases.

Look carefully at this pedigree, there are no affected males, only affected females. Living females outnumber living males two to one when the mother is affected