1. Mutations, Mitosis, Meiosis, & Genetics
HOW are they related??

2. Mutation A change in the nucleotide sequence of DNA.
May involve a single nucleotide or may involve many nucleotides
WHAT is the effect of a mutation? It may change the PROTEIN the gene encodes!

3. Mutations, cont Can changing only 1 nucleotide really matter? YES!!
Mutations may be harmful, beneficial, or unnoticeable to the organism

4. Types of Mutations:
1. Base substitutions: replacement of one nucleotide with another in the DNA of a gene;
Effect depends on whether there is an amino acid change that alters the function of the protein

5. Base Substitution (or Point Mutation), cont.
Change the underlined A to a C
Corr: ATA GAT TAC ACG
tyr leu met try
Mut: ATA GAT TAC CCG
tyr leu met gly
As above, RESULT MAY be a Coding Change in 1 amino acid of the protein.

6. Base Substitution, cont.
Normal hemoglobin DNA
Mutant hemoglobin DNA
mRNA
mRNA
Figure 10.16A The molecular basis of sickle-cell disease.
This figure shows the base pair change that leads to the formation of sickle cell hemoglobin. This results in an amino acid change in the protein, from glutamic acid to valine. This substitution of a hydrophobic amino acid for a hydrophilic one causes a significant difference in the activity of the -hemoglobin chain. Normal hemoglobin molecules exist as individual units whether they are bound to oxygen or not. Sickle cell hemoglobin molecules are also single entities when oxygen is bound, but they form large polymers that distort the shape of the cell when oxygen is released to the tissues. The cells may have an irregular appearance or assume the crescent or sickle shape for which the disease is named. These misshapen cells tend to clog blood vessels, leading to pain, infection, and damage to organs. Cells with sickle cell hemoglobin have a shorter lifetime than normal cells (10–20 days as opposed to 3 months) so anemia sets in because the bone marrow is unable to produce new cells as rapidly as they are removed from the population. This example demonstrates that a seemingly small change, a difference of one base pair leading to a change in a single amino acid (out of 147), can have severe effects.
Normal hemoglobin
Sickle-cell hemoglobin
Glu
Val

7. Do Base Substitutions ALWAYS result in a coding change?
NO- change of 1 nucleotide in DNA does NOT always change the amino acid or protein
Ex: CAA  CAC
Both code for “valine” (VAL)
What position of codon is changed? This is a Silent Mutation (NO coding change occurs!)

8. Mutations, cont.
2. Deletions or insertions: Adding or removing a nucleotide(s) in the coding sequence
Alters the “reading frame” of the mRNA, so that nucleotides are grouped into different codons “downstream” of change – a FRAMESHIFT!
Usually results in significant changes in amino acid sequence downstream of mutation; results in a nonfunctional polypeptide!

9. What do we mean by “Reading Frame” & Frameshift??
Compare the sentences of 3 letter words:
THE CAT ATE THE HOT DOG
What happens if we lose the C?
THE ATA TET HEH OTD OG
Does that make sense??? NO!! It is a Frameshift!!

10. Frame Shift
When the “reading frame” of the gene changes, codons are changed and amino acids are different AFTER the deletion/ insertion.
Radically changes structure & sequence of the protein

11. Deletion (& Frameshift)
1 or more nucleotides removed from DNA coding sequence;
Ex: DNA TAC GGA TCT AGG ACT
mRNA AUG CCU AGA UCC UGA
met pro arg ser stop
(start)
Delete the first G; how does this change the amino acids? Does it change 1 or many AA?

12. Deletion & frameshift, cont.
Does it change 1 or many AA?
DNA: TAC *GAT *CTA *GGA *CT
mRNA AUG *CUA *GAU *CCU *GA
Met *leu *asp *pro
(Original: Met-Pro-Arg-Ser-stop)
* Changed codons AND amino acids!

13. Insertion (& Frameshift)
1 or more bases are added (inserted!) to the DNA coding sequence;
Add G after the first codon below:
GGC ACG TAT CTA TCG
GGC GAC GTA TCT ATC G
As in case of deletions, USUALLY results in a reading frame shift.
When does an insertion OR deletion change ONLY 1 amino acid?

14. Normal gene mRNA Protein Base substitution Base deletion Missing Met
mRNA
Protein
Met
Lys
Phe
Gly
Ala
Base substitution
Met
Lys
Phe
Ser
Ala
Figure 10.16B Types of mutations and their effects.
This figure contrasts the multiple amino acid changes caused by a deletion with the single amino acid change caused by a substitution.
Base deletion
Missing
Met
Lys
Leu
Ala
His

15. Another possible result: Early Stop mutation
Can happen as a result of a nucleotide change, deletion, or insertion
An early stop codon occurs in the transcript, so the protein is shorter than normal.

16. What causes mutations? Random changes during DNA replication
Mutagens-environmental factors that cause mutations
Carcinogens-environmental factors that cause mutations that lead to cancer

17. Can you reduce your risk?
YES!!!
Screening for early detection
Avoid tobacco products
Healthy, balanced diet
Wear sunscreen
Get regular exercise

18. Are all mutations BAD? NO!!
One KEY reason mutations are good: introduce change into the genome! This is necessary for evolution to occur!!

19. Cell Division Why do cells NEED to divide?
Is there only 1 type of division?
NO- there are 2 types of cell division for different purposes!

20. How did we ALL begin? As ONE cell- the fertilized egg (zygote)!!
How did we become a baby?
Cell division!!
What does that mean? Mitosis!

21. Mitosis The process where one cell divides into 2 identical cells
This is how 1 cell became millions of cells in an adult!
It is also HOW we grow & repair our bodies.
What has to happen BEFORE mitosis can occur?

22. Answer: DNA replication!
All 46 chromosomes (in humans) have to be copied so both DAUGHTER cells get the same 46 chromosomes that were in the parent cell.

23. Parent cell
Chromosomes are copied and double in number (sister chromatids are attached at by the centromere
Chromosomes now split
2 daughter cells identical to original

24. Animation of mitosis:

25. So, we’ve got 46 chromosomes.
How many different PAIRS of chromosomes do we have?
23 pairs of chromosomes
How are Males & Females GENETICALLY different??
Females have 2 X chromosomes
Males have 1 X and 1 Y chromosome- presence of Y makes you a male!!

26. What are diploid and haploid for us?
CHROMOSOME NUMBER
Diploid: A pair (2 copies) of each different chromosome; most body cells are diploid;
diploid = 2n (where n is the number of different chromosomes)
The number of chromosomes in egg and sperm cells (gametes) is haploid which is “n”, or 1 copy of each different chromosome
What are diploid and haploid for us?

27. Answer:
Diploid= 46chromosomes =2 copies of 23 different chromosomes ( XX or XY)
Haploid = 1 copy of 23 different chromosomes ( X or Y)

28. Where does each chromosome of the pair come from. (Ex
Where does each chromosome of the pair come from? (Ex. You’ve got 2 copies of chr 1- where did each copy come from?)
One chromosome comes from MOM, and one chromosome comes from Dad

29. So, who determines the sex of a baby????
DAD- He is the ONLY parent that can contribute the Y chromosome that makes the fetus male.

30. How do the gametes (sex cells) end up with only 23 chromosomes
How do the gametes (sex cells) end up with only 23 chromosomes? THINK MEIOSIS!!
WHY do they need to be haploid (only 1 copy of each chromosome or 23 total chromosomes)?

31. IT’S ALL ABOUT SEXUAL REPRODUCTION…
MEIOSIS
IT’S ALL ABOUT SEXUAL REPRODUCTION…

32. MEIOSIS
A type of cell division where the number of chromosomes is reduced by half
ONLY occurs in gonads (ovaries or testes) during formation of gametes (egg or sperm)
Human body cells have 46 chromosomes; human sperm and egg cells each have 23 chromosomes

33. Gametes are haploid for SEXUAL REPRODUCTION!
When egg and sperm combine during fertilization, each brings half the total number of chromosomes for that species
Half + half = whole
In humans, 23 chromosomes (from Dad) + 23 chromosomes (from Mom) = 46 chromosomes (child) !!!

34. FERTILIZATION egg + sperm = zygote 23 + 23 = 46 n n 2n
= 46
n n 2n
Haploid haploid = diploid

35. Summary of Meiosis
Type of cell division used to form the gametes (egg & sperm) where chromosome number is reduced to haploid (n).
Chromosomes assort RANDOMLY so each gamete is unique! This increases biodiversity of species.
It involves 2 cell divisions, NOT 1 like in mitosis.
Results are 4 haploid daughter cells!

36. Animation of Meiosis

37. MORE ABOUT CHROMOSOMES
In humans, there are 22 different “regular” chromosomes (numbered 1 to 22 by size & shape) and 2 different sex chromosomes
The sex chromosomes are X and Y
Which sex chromosomes are in a girl? XX
Which are in a boy? XY

38. Karyotype A photograph of all of an organisms chromosomes.
Scientists freeze cells at the metaphase of mitosis. At this stage, chromosomes are easy to isolate and stain.

39. What to look for in a Karyotype?
When analyzing a human karyotype, scientists first look for these main features:
1. Are there 46 chromosomes?
2. Are there 2 identical pairs of each autosome and 2 sex chromosomes?
3. Are there any rearrangements between chromosomes or large deletions?

40. Why perform a karyotype?
Verify chromosome number (some genetic diseases are caused by MORE copies of a chrom.)
Confirm chromosome shape, structure and size.

41. Down’s Syndrome Karyotype (Trisomy 21)

42. ALL HUMANS HAVE THE SAME GENES ON THE SAME CHROMOSOMES!
If mom’s chromosome #1 carries the genes for eye color, hair color, and height, then dad’s chromosome #1 also carries the genes for eye color, hair color, and height
Each chromosome of the pair contains an ALLELE (or copy) of every gene.

43. Different versions of the same Gene are known as ALLELES!!
CHROMOSOME PAIR #1
BLUE EYES
BROWN HAIR
TALL
BLUE EYES
BLOND HAIR
SHORT
= A GENE (allele) ON A CHROMOSOME

44. What is Phenotype? What is Genotype? Outward expression of an allele
(how it looks- PHYSICAL)
Ex.: Blue or Brown eyes, Tall or short, Artistic, Athletic
What is Genotype?
Genetic makeup (the GENES) of an organism
Ex. Ff, FF, ff

45. DOMINANCE
Some genes are “stronger” than others; they are called dominant
The weaker gene is recessive
EXAMPLES:
BROWN EYES ARE DOMINANT OVER BLUE EYES- A person may have BOTH genes, but we ONLY see the Brown eyes
Tall is DOMINANT OVER short

46. In many cases, one gene is NOT stronger than the other.
This is called Incomplete
Dominance
This can cause a MIXED phenotype-
For Ex.: Incomplete dominance of the gene for red and white flower color will result in PINK flowers.

47. Combinations of alleles
FF and ff are Homozygous for the genes and traits
FF= homozygous dominant; phenotype is DOMINANT trait
ff = homozygous recessive; phenotype is RECESSIVE trait

48. Combinations of alleles
Ff is Heterozygous for the genes (genotype).
If F is dominant, a person who is Ff will look the SAME as someone who is FF (different genotype, same phenotype!)

49. Example: F= dominant= fuzzy seed & f= recessive= smooth seed
What are the genotype and phenotype for homozygous dominant?
What are the genotype and phenotype for homozygous recessive?
What are the genotype and phenotype for heterozygous?
Cross Ff x Ff (Punnett Sqare)

50. Answers: Homozygous dominant= FF= fuzzy
Homozygous recessive= ff= smooth
HETEROZYGOUS= Ff= fuzzy

51. How do we track who has a trait in a family- a Pedigree!
A chart that shows how a trait and the genes that control it are inherited within a family.
A ‘family tree’ for a genetic trait or disease.

52. Pedigree symbols

55. Cystic Fibrosis Pedigree (recessive)

56. Cystic Fibrosis Pedigree

57. What if a trait is carried on the X chromosome?
It is called a sex-linked trait.
Will it be inherited the SAME as trait on an autosomal (numbered) chromosome?
NO- because the Male only has 1 copy, and he gets it ONLY from MOM!!!!

58. Sex-linked recessive allele (haemophilia, red-green color blind)

59. Sex-linked recessive, cont.

60. Sex-linked, cont.

61. Pedigree
Summary: Pedigrees help determine the inheritance of some alleles and predict them in offspring.

62. How do we PREDICT which traits an offspring will inherit?
A Punnett square!!!
Put MOM’s 2 genes (alleles) on the top; Dad’s 2 genes (alleles) on the side
Match up the possibilities in every square.
For 1 trait, there are 4 possible offspring!

63. Our genes determine a LOT of who we are (but NOT everything)
Have you ever noticed that certain traits run in families? Like musical ability, athletic, mechanical ability, more intellectual, etc.
Our genes determine a LOT of who we are (but NOT everything)
What we are good at- sports, music, schoolwork
Our height, eye color, hair color
personality traits

64. Do Chromosomes ever change?
YES! Changes can occur in the chromosome (a BIG change- deletion, repeat, extra copy) or in the sequence of the DNA (LITTLE change- switch the nucleotide base (letter); delete 1 or more bases; insert extra 1 or more bases).
Both these types of changes are called MUTATIONS.

65. What MAY happen when there is a mutation in the DNA or chromosome?
The offspring may develop a GENETIC DISEASE.
How is a GENETIC DISEASE (like cystic fibrosis) different from an INFECTIOUS DISEASE (strep throat)?

66. Write down these terms:
Mitosis
Meiosis
Diploid
Haploid
Sex chromosomes in a Male?
Sex chromosomes in a Female?
Number of chromosomes in a person?
Karyotype
Allele
Genotype
Phenotype
Dominant
Recessive
Homozygous
Heterozygous
Pedigree