Molecular Genetics

1. Molecular Genetics

2. Structure of DNA Nucleotides: Nucleic acids are formed from two long chains of these individual units. They are made of A phosphate group + a sugar (deoxyribose) + a nitrogen base • There are four different nitrogen bases in DNA: Adenine (A) Guanine (G) Cytosine (C) Thymine (T)

3. DNA has a double helix structure. When unwound it supposedly looks like a ladder • The sugar - phosphate pieces of the nucleotide form the “sides” of the ladder, while the nitrogen bases from the rungs or hand rails of the ladder.

4. Deoxyribonucleic acid (DNA)

5. The four bases (ie adenine, thymine, cytosine and guanine) are separated into two groups: 1. The purines (adenine and guanine) have a double ring structure 2. The pyrimidines (thymine and cytosine) have a single ring structure

6. The bases make complementary base pairings. (A)denine matches with (T)hymine (G)uanine matched with (C)ytosine The phosphate backbones (the sides of the ladder) in DNA run opposite to one another or antiparallel to one another.

7. Question: What DNA strand is complementary to CAGTACTTCGA?

8. RNA(Ribonucleic Acid) • Stands for ribonucleic acid • Has a structure very similar to DNA except • 5carbon sugar is ribose, not ____________. • The nitrogenous base uracil (U) takes the place of thymine (T)

9. The DNA code • Recall that DNA is in the form of a twisted ladder having phosphate and sugar for it’s sides and nitrogenous bases for it’s ladder rungs. The rungs are held together by hydrogen bonds.

10. DNA Replication DNA replicates in a semi-conservative way.

11. There are four main stages of DNA replication: 1. Initiation (a portion of the double helix is unwound) – This is where the two sides of a DNA strand are unwound and unzipped. 2. Elongation (when two new strands of DNA are assembled 3. Termination (new DNA forms into helices) 4. Proofreading and correction

12. Protein Synthesis Proteins are made up of 20 kinds of amino acids. Linked amino acids from long chains called Polypeptides. Therefore polypeptides form proteins

13. Amino acids are coded by a sequence of “3 base words” or 3 bases of the DNA strand. Eg. CGA – the amino acid glycine

14. Stages of Protein synthesisPart 1 - Transcription Transcription is the copying of a genetic message from DNA to mRNA. 1. DNA molecule splits apart in the nucleus of the cell 2. Messenger RNA (mRNA) nucleotides enter the nucleus and attach to the DNA molecule in their complementary positions. 3. A strand of mRNA is formed on the DNA molecule 4. mRNA breaks away from the DNA molecule and leaves the nucleus.

15. Each group of 3 bases on the mRNA is called a codon • By lining up against the DNA molecule, the RNA nucleotide form a strand of mRNA which is a perfect copy of the genetic information in the DNA

17. Part 2 - Translation Protein synthesis occurs in the cytoplasm of the cell. Here, there is a good supply of the owning acids needed to make proteins. Here’s how it works: 1. tRNA molecules attach to their appropriate amino acid carrying an anticodon. 2. Ribosomes attach to the mTNA milecule.

18. The tRNA temporarily joins to the mRNA, bringing with it, it’s amino acid. 4. As more tRNA molecules come in to the mRNA, the old tRNA leave, but the amino acid molecules stay behind and form a chain. This chain eventually becomes a polypeptide. 5. The process whereby a ribosome moves the mRNA molecule along to attach it to a series of tRNA molecules to from an amino acid chain is called Translation.

19. Environment vs. Genetics in Gene Expression When the DNA of a person’s genes are transcribed and translated during the process of protein synthesis, it directs the building of new cells, tissue, organs, systems, and eventually people. The way we “turn out” is therefore largely affected by our DNA.

20. Q. What other factors affect the characteristics of offspring? The environment can also have a large role in determining the characteristics of offspring. A human, for example, may have the genotype to grow to be 6 feet tall, but if s/he is raised without proper nutrition, their height may reach only 5’5”.

21. Another example involves a species of reptile in which the incubation temperature determined the sex of the offspring. High temperatures produce males, low temperatures produce females.

22. Mutations Q. What happens if a gene or chromosome is partly changed? Definition: A mutation is a sudden change in the structure or the amount of genetic material Eg. May result in a sudden change in the structure or the amount of genetic material.

23. There are 2 main types of mutations: 1. Chromosomal mutations – a change in the structure or number of chromosomes. eg Down’s Syndrome 2. Gene mutation – a change affecting a gene on a chromosome. Eg. White eyed male fruit fly.

24. Types of gene mutations Point mutations (gene mutations) involve small changes in nucleotide sequence within individual genes. They are separated in to two groups 1. Substitution mutations 2. Frame shift mutations

25. Substitution mutations • There are three types of substitution mutations. 1. silent mutation – A mutation that has no effect on the cell’s metabolism. See figure 17.32

26. 2. mis-sense mutations – type of mutation that alters the make up of a protein. This can be serious. Eg. People with mutations of one amino acid in the proteins that makes up hemoglobin is responsible for sickle cell disease. Eg. Figure 17.32 3. nonsense mutation – A mutation that renders the gene unable to code for any functional polypeptide product. Eg. Fig 17.32

27. Frameshift Mutations 1. Insertion – The insertion of nucleotides that can cause the reading of the mRNA to be totally altered 2. Deletion – The deletion of nucleotides that can cause the reading of the mRNA to be totally altered.

28. Jumping genes • Jumping genes are also known as transposons. These are short strands of DNA capable of moving from one location to another within a cell’s genetic material. • This happens in the case of Indian corn. • Barbara McClintock first discovered jumping genes in 1957.

29. Types of Chromosomal Mutations • During meiosis, there are several things which can go wrong with chromosomes. They may become tangled and their parts may be re-arranged. Such changes can have serious effects on heredity. Here are some of the things that can go wrong: 1. Translocation – The transfer of part of a chromosome to a non-homologous chromosome 

30. 2. Inversion – a piece of a chromosome is rotated reversing the order of the genes. 3. Addition – a piece of a chromosome breaks off and attaches to a homologous chromosome. 4. Deletion – Part of a chromosome breaks off…..some of the genes are lost 5. Nondisjunction – Extra chromosomes – eg trisomy 21.

31. Human Disorders Caused by Chromosomal Mutations • Down Syndrome (aka trisomy 21): Nondisjunction of the 21st pair of chromosomes. There is an extra copy of the 21st chromosome. People are characteristically broad and short, large tongues. • Klinefelter Syndrome (XXY): nondisjunction of sex chromosomes. Results in a male with an extra X chromosome. Patients develop breasts, high-pitched voices, sterile and below normal intelligence.

32. Turner syndrome: (Y chromosome missing): Produces females that at first seem “normal”. They never fully develop breasts, or sex organs and are sterile. • Jacob syndrome (XYY): Nondisjunction where males have an extra Y chromosome. Tend to be little taller. No real ill effects.

33. Triple X syndrome (XXX): Female has an extra X chromosome. Symptoms vary, but can include infertility, tall stature, delayed puberty, among others.

34. Human Genetics Autosomal Recessive disorders: • Tay-Sachs disease – By 8 months babies start to deteriorate mentally. Most die at or before age 5. • Phenylketonuria (PKU) – If not diagnosed at birth, it can cause children to be severely mentally handicapped within months.

35. Codominant inheritance: • Sickle cell anemia – Defect in the red blood cells that causes them to clot easily. People that are

36. Autosomal dominant inheritance: • Progeria – individuals with this disease age very rapidly and die at a young age. • Huntington disease – Causes mental deterioration usually starting at about age 35.

37. Incomplete dominance: • FH (familial hypercholesterolemia) – People with this disease tend to have twice the amount of cholesterol in their systems.

38. X – linked Recessive Inheritance: • Colour blindness – Person cannot distinguish between red and green. • Muscular Dystrophy – All muscles in the body deteriorate. • Hemophilia – Persons blood doesn’t clot normally.