Topic 2 & 3: Genetics Review

Syllabus Statements2.4.1 Outline DNA nucleotide structure in terms of sugar (deoxyribose), base and

phosphate.2.4.2 State the name of the 4 bases in DNA2.4.3 Outline how the DNA nucleotides are linked together by covalent bonds into a

single strand.2.4.4 Explain how a DNA double helix is formed using complimentary base pairing and

hydrogen bonds.2.4.5 Draw a simple diagram of the molecular structure of DNA.2.5.1 State that DNA replication is semi-conservative.2.5.2 Explain DNA replication in terms of unwinding of the double helix and separation

of the strands by helicase, followed by formation of the new complementary strand by DNA polymerase.

2.5.3 Explain the significance of complementary base pairing in the conservation of the base sequence of DNA.

2.6.1 Compare the structure of RNA and DNA2.6.2 Outline DNA transcription in terms of the formation of an RNA strand

complementary to the DNA strand by RNA polymerase.2.6.3 Describe the genetic code in terms of codons composed of triplets of bases.2.6.4 Explain the process of translation, leading to peptide linkage formation.2.6.5 Define the terms degenerate and universal as they relate to the genetic code.2.6.6 Explain the relationship between one gene and one polypeptide.

Outline DNA nucleotide structure in terms of sugar (deoxyribose), base and phosphate.

Nucleotide

Four DNA bases areThyamineAdenineCytosineGuanine

Outline the bonding in the DNA strand

Covalent bond

Structural Details

Antiparallel Strands Complementary Base Pairing

What is meant by semiconservative replication of DNA?

Complementary base pairing ensures that resulting strands are equal to initial

How Does replication happen?

a) Helicase: which unwinds the DNA double helix and separates the strands by breaking the hydrogen bonds

b) DNA Polymerase which links up the nucleotides to form the new strand of DNA.

This 2nd step, after the unwinding and separation of strands, involves having the single strands act as templates for the new strands.

Free nucleotides are present in large numbers around the replication fork. The bases of these nucleotides form hydrogen bonds with the bases of the parent strand. DNA polymerase is the main enzyme involved.

Daughter DNA molecules each rewind into a double helix.

List 3 ways RNA is different from DNA

a) RNA nucleotides contain the sugar ribose. Ribose has one more hydroxyl than deoxyribose.

b) Uracil, a pyrimidine, is unique to RNA and is similar to thymine (A, C, G, U).

c) RNA is single stranded.

Transcription

What is a codon?

• A 3 base sequence in mRNA

• Each codes for a particular amino acid

• 64 possible codons• 20 amino acids• Stops & starts also

Define

• Degenerate – Amino acids are coded for by multiple

different codon sequences. As many as 6 sequences in some cases for one amino acid

• Universal – DNA code is the same in all living things. The

gene for a bacterial polypeptide will create the same polypeptide in any eukaryote

Translation Initiation

Translation Elongation

Translation Termination

So Here’s a DNA Strand

ATTCGGCCACATTTC

1. Write out the complementary strand

TAAGCCGGTGTAAAG

2. Write out the RNA transcript of the original strand

UAAGCCGGUGUAAAG

3. Write out the first 3 tRNA anticodons

AUU CGG CCA

Syllabus Statements

• 3.1.1: State that eukaryotic chromosomes are made of DNA and protein

• 3.1.2: State that in karyotyping chromosomes are arranged in pairs according to their structure

• 3.1.3: Describe one application of karyotyping (cross reference with 3.2.5)

• 3.1.4: Define gene, allele, genome• 3.1.5: Define gene mutation• 3.1.6: Explain the consequence of a base

substitution mutation in relationto the process of transcription & translation, using the example of sickle cell anemia

• Chromosomes = composed of DNA and histone proteins in eukaryotes

Definitions

• Gene =

• Allele =

• Genome =

• Gene mutation =

Human Karyotype

• Can display an individual’s somatic-cell metaphase chromosomes

• Karyotype when arranged in a standard sequence.

• Display of chromosomes arranged by size, position of centromere and staining pattern.

• Often made from lymphocytes or amniocytes.

Sickle Cell Disease

Sickle Cell Disease

• Replacement of #6 amino acid, glutamic acid, with valine substitutes a non-polar amino acid for a polar amino acid.

• #6 amino acid is on the OUTSIDE of the hemoglobin molecule.

• Hydrophobic interaction set up by valine causes change in shape of hemoglobin which leads to sickling of the red blood cell.

Syllabus Statements II• 3.3.1: Define genotype, phenotype, dominant

allele, recessive allele, codominant alleles, locus, homozygous, heterozygous, carrier, test cross

• 3.3.2: Construct a Punnett grid• 3.3.3: Construct a pedigree chart• 3.3.4: State that some genes have more than two

alleles (multiple alleles)• 3.3.5: Describe ABO blood groups as an example

of codominance and multiple alleles• 3.3.6: Outline how sex chromosomes determine

gender by referring to the inheritance of X and Y chromosomes in humans

Some Definitions

Dominant allele =

Recessive allele =

Codominant alleles =

Locus =

• 3.3.7: State that some genes are present on the X chromosome and absent from the shorter Y chromosome in humans.

• 3.3.8: Define Sex linkage• 3.3.9: State two examples of sex linkage• 3.3.10: State that human females can be

homozygous or heterozygous• 3.3.11: Explain that female carriers are

heterozygous for X-linked recessive alleles• 3.3.12: Calculate and predict the genotypic and

phenotypic ratios of offspring of monohybrid crosses involving any of the above patterns of inheritance

• 3.3.13: Deduce the genotypes or phenotypes of individuals in pedigree charts

Figure 14.4 Mendel’s law of segregation (Layer 2)

Terms from Crosses1. Homozygous: Having 2 identical alleles for

a given trait• True breeding, all gametes carry same allele

2. Heterozygous: Having 2 different alleles for a given trait

• Not true breeding, half of gametes carry one allele, half carry the other

3. Phenotype: An organism’s expressed traits• F2 phenotypic ratio of 3:1 = 3 purple, 1 white

4. Genotype: An organism’s genetic make up• F2 genotypic ratio of 1:2:1 = 1PP, 2Pp, 1pp

Test Crosses

Test Cross: Breeding an organism of unknown genotype with one that is known homozygous recessive

e.g. P__ X pp : if all progeny purple, then ___

: if ½ purple, ½ white, then ___

Figure 14.9 Incomplete dominance in snapdragon color

Multiple Alleles

• More than 2 alternate forms of a gene• E.g. = ABO blood group; produce 4 possible

phentypes (A, B, AB, O)• A & B are 2 genetically determined

polysaccharides (A & B antigens) found on the surface of RBC

• Three alleles for this gene: IA (A antigen), IB (B antigen), and i (no antigen)

• Alleles IA & IB are codominant, and dominant to i

Figure 14.10 Multiple alleles for the ABO blood groups

Pedigree Rules

• By convention squares represent males

• Circles represent females

• Shaded symbols indicate individuals showing the trait

• Horizontal line connecting male and female signifies reproduction (or marriage)

• Offspring are listed below in birth order

Generally

• If a mother & father do not show a trait but they have an offspring that does – usually this indicates recessive inheritance

• If males show a trait more than females and / or mothers pass the trait to their sons it is generally sex linked inheritance

• Otherwise its dominance inheritance – only specific example we discussed of this was huntington’s chorea

Practice Problem

Sex linkage

• Sex linkage: In addition to determining sex, the X and Y chromosomes contain many genes not related to sex

• In humans sex linkage is usually equivalant to X-linkage

• Examples– Colorblindness: Xb presence relative to the

normal XB

– Hemophilia: Xh presence relative to the normal XH

Hemophilia

• A man with hemophilia ( a recessive, sex linked condition Xh) has a daughter of normal phenotype. She marries a man who is normal for the trait

1. What is the probability that the daughter of this mating will be a hemophiliac?

2. What is the probability for a son?

3. If the couple has 4 sons, what is the probability that they will all be born with hemophilia?

Solution

• P generation (man) = (XH XH) x (XhY)

• F1 generation (daughter) = (Xh XH) x (XHY)

1. 0%

2. 50%

3. ½ * ½ * ½ * ½

= 1/16

XH Y

XH XH XH XHY

Xh XH Xh XhY

Red-green Color Blindness

• Red-green Color Blindness is caused by a sex-linked recessive allele (Xb). A color blind man marries a woman with normal vision whose father was color blind.

1. What is the probability that they will have a color blind daughter? (this is 2 events 1st daughter, then color blind)

2. What is the probability that thir first son will be color blind?

Solution

• Color blind man = XbY• Woman = XBXb

• P generation = (XBXb) x (XbY)

1. ¼

2. ½

Xb Y

XB XB Xb XBY

Xb Xb Xb XbY

Sex Linkage: General Statements

1. Fathers pass X-linked alleles to only and all of their daughters

2. Fathers cannot pass X-linked traits to their sons

3. Females receive 2 X chromosomes, one from each parent

4. Mothers pass only 1 X chromosome (either maternal or paternal homologue) to every daughter and son

5. If a sex linked trait is due to a recessive allele, a female will express that trait if and only if she is homozygous

Syllabus Statements• 3.2.1 State that meiosis is a reduction division in terms of

diploid and haploid numbers of chromosomes.• 3.2.2 Define homologous chromosomes• 3.2.3 Outline the process of meiosis, including pairing of

chromosomes followed by two divisions, which results in four haploid cells.

• 3.2.4 Explain how the movement of chromosomes during meiosis can give rise to genetic variety in the resulting haploid cells.

• 3.2.5 Explain that non-disjunction can lead to changes in chromosome number, illustrated by reference to Down’s syndrome (trisomy 21).

• 3.2.6 State Mendel’s law of segregation. (Done with genetics)• 3.2.7 Explain the relationship between Mendel’s law of

segregation and meiosis (Done with genetics)

Sexual vs. Asexual Reproduction

• Asexual: 1 individual is sole parent

• Single parent passes on all its genes to offspring

• Offspring genetically identical to parent

• Results in clone; rarely, genetic differences occur as a result of mutation, a change in the DNA

• Sexual: 2 parents give rise to offspring

• Each parent passes on ½ its genes to offspring

• Offspring have unique combination of genes

• Results in greater variation; offspring vary genetically from sibs and parents

• Adaptive to changing environments

Definitions5. Homologous Chromosomes: a pair of

chromosomes that have the same size, centromere position and staining pattern.

With one exception, homologues carry the same genetic loci.

X and Y chromosomes pair during meiosis but Y is much smaller.

6. Autosome: chromosome that is not a sex chromosome.

7. Sex chromosome: dissimilar chromosomes that determine an individual’s sex.

Chromosomal pairs in the human karyotype are a result of our sexual origins: 1 homologue is inherited from each parent

Mitosis vs. Meiosis

Chromosomal Non-disjunction and Down Syndrome: Errors in

Meiosis• Sometimes chromosomes fail to disjoin during

either Meiosis I or Meiosis II. Instead they move to the same pole.

• Non-separation of chromosomes is called non-disjunction and results in gametes with either one chromosome too many or one chromosome too few (frequently lethal).

• Gametes with 2 doses of a chromosome that join with a gamete with the normal dose of chromosomes now have 3 doses of this chromosome (trisomy).

Nondisjunction in Meiosis I and II

Syllabus Statements3.4.1 State that PCR copies and amplifies minute quantities of nucleic acid3.4.2 State that gel electrophoresis involves the separation of fragmented pieces of

DNA according to their charge and size.3.4.3 State that gel electrophoresis of DNA is used in DNA profiling.3.4.4 Describe 2 applications of DNA profiling.3.4.5 Define genetic screening.3.4.6 Discuss 3 advantages and/or disadvantages of genetic screening.3.4.7 State that the Human Genome Project is an international cooperative venture

established to sequence the complete human genome.3.4.8 Describe two possible advantageous outcomes of this project.3.4.9 State that genetic material can be transferred between species because the

genetic code is universal.3.4.10 Outline the basic technique used for gene transfer involving plasmids, a host

cell (bacterium, yeast or other cell), restriction enzymes (endonuclease) and DNA ligase.

3.4.11 State 2 examples of the current uses of genetically modified crops or animals.

3.4.12 Discuss the potential benefits and possible harmful effects of 1 example of genetic modification.

3.4.13. Outline the process of gene therapy using a named example.3.4.14 Define clone.3.4.15 Outline a technique for cloning using differentiated cells.3.4.16 Discuss the ethical issues of cloning in humans.

Explain the Following Techniques

• What does PCR do?

- copies and amplifies minute quantities of nucleic acid

• What does gel electrophoresis do?

-separation of fragmented pieces of DNA according to their charge and size.

- used in DNA profiling

What are some of the Applications of DNA Profiling?

1. Forensic use

2. Diagnosis of genetic disorders.

3. Identifying individuals who died long ago.

4. Identifying animals that migrate in order to estimate population size.

5. Identifying animal parts (distinguish from common species vs. endangered species).

Contamination of samples by even a single cell would totally throw off results.

What is Genetic Screening?.

Advantages: 1. Fewer children with genetic

diseases are born because people choose not to have children or choose a partner who is not a carrier for the same allele.

2. Frequency of alleles causing genetic disease can be reduced.

3. Genetic disease can be found and treated more effectively (e.g. PKU, Galactosemia)

Disadvantages:1. Frequency of abortion may

increase.2. Harmful psychological effects

may result from knowing that you are a carrier/at risk of a genetic disease.

3. Creation of a genetic underclass (think of the movie Gataca): refusal of jobs, life insurance, health insurance; less likely to find a partner.

Testing of an individual for the presence or absence of a gene

What is the Human Genome Project

- an international cooperative venture established to sequence the complete human genome.

• Sequenced 3 billion bases and found 30,000 genes.

• Could lead to an understanding of many genetic diseases and how genes control human development.

• Could lead to the development of genomic libraries and the production of gene probes to detect sufferers and carriers of genetic disease.

• Allows the production of pharmaceuticals based on DNA sequences (Designer drugs).

Describe the basic technique of gene transfer

List examples of GMO

a) Salt tolerance in tomato plants; delayed ripening in tomatoes, frost resistance in tomatoes (trout gene).

b) Herbicide resistance in crop plantsc) Factor IX (human blood clotting factor) formed in

sheep milkd) transfer from cattle to chickens a gene for making

growth hormone.e) Transfer of gene for human insulin to bacteria.f) Transfer of frost resistance gene from trout into

tomato.

What are the potential risks & benefits of GM? Bt Corn example

1) Less pest damage; higher crop yields, reduction of food shortages.

2) Less land needed for crop production, more for wildlife conservation.

3) Less use of insecticide sprays which harm farm workers and wildlife.

1. Humans or farm animals could eat genetically modified maize and be harmed by bacterial DNA or Bt toxin.

2. Other non-pest insects could be killed e.g. pollen blown distances kill monarch butterfly caterpillars.

3. Engineered crops could cross species barriers. Escape and spread and compete with naturally occurring varieties.

Outline the process of gene

therapy

What is a clone?

A clone is a group of genetically identical organisms or a group of cells artificially derived from a single parent cell.

Outline the process of cloning differentiated cells

Step 1: Udder cells were taken from a donor sheep. Cells were cultured in low nutrient broth to make them switch off their genes and become dormant.

Step 2: Unfertilized egg cells were taken from another sheep and the nucleus removed from each egg cell using a micropipette.

Step 3: Enucleate egg cells were fused with donor cells using a pulse of electricity.

Step 4: Fused cells developed like zygotes and became embryos which were implanted into another sheep who became the surrogate mother.

Step 5: Lamb born was genetically identical to sheep whose udder cells were used.

Is it right or wrong to clone humans?