1. Genes and DNA replication

2. Meiosis – Greek for reduction

3. About 2000 genes per chromosome
Gene – instructions for making proteins

4. Roles of DNA, RNA & Proteins
46 chromosomes in the nucleus of every somatic cell
1. 23 homologous (matching) pairs of chromosomes
2. each chromosome is composed of over genes

5. Each gene (“axon” segment) on a chromosome specifies the amino acid sequence of 1 specific protein (“trait”)

6. 1. most genetic mutations (changes) are harmful because it causes defective proteins to be produced
a. these are called genetic (“in-born”) diseases
b. includes: cystic fibrosis, hemophilia, Tay- sachs, albinism, late-onset diabetes, cancer

7. 2. Functions of proteins in the body
a. structural proteins – collagen, keratin
collagen – dermis of the skin, ligaments
keratin – nails, hair
b. protein hormones – insulin, glucagon, oxytocin, growth hormone
c. contractile proteins – actin, myosin

8. d. antibodies – (immunoglobulins, “gamma- globulins”)
e. transport proteins (ex. Hemoglobin, HDL, LDL)
* HDL, LDL – lipoproteins
HDL = healthy
LDL = lethal, transports cholesterol to the walls of the arteries causing atherosclerosis

9. f. enzymes – proteins that catalyze biochemical reactions
g. “tumor suppressor” genes – ex. P53 gene specifies proteins that inhibit cell division (mitosis)
mutation of p53 gene – colon cancer
mutation of BRCA gene – breast cancer

10. * Pharmacogenetics

11. DNA Replication
A. occurs in cells before they can divide into 2 cells (mitosis)
The DNA unzips (Helicase) down the middle so that each strand acts as a structural pattern (“template”) to reconstruct a new complementary strand for its half

12. DNA + DNA Polymerase + DNA nucleotides + ATP = DNA copies

13. Transcription (“making a copy” of a gene): Synthesis of RNA
A. occurs in cells before they can synthesize proteins
The portion of a DNA specifying one protein unzips down the middle so that 1 strand acts as a structural pattern (“template”) to construct a complementary RNA strand for its half

17. The Structure of DNA
DNA is composed of four nucleotides, each containing: adenine, cytosine, thymine, or guanine.
The amounts of A = T, G = C, and purines = pyrimidines [Chargaff’s Rule].
DNA is a double-stranded helix with antiparallel strands [Watson and Crick].
Nucleotides in each strand are linked by 5’-3’ phosphodiester bonds
Bases on opposite strands are linked by hydrogen bonding: A with T, and G with C.

18. The Basic Principle: Base Pairing to a Template Strand
The relationship between structure and function is manifest in the double helix
Since the two strands of DNA are complementary each strand acts as a template for building a new strand in replication

20. DNA replication
The parent molecule unwinds, and two new daughter strands are built based on base-pairing rules
(a) The parent molecule has two complementary strands of DNA Each base is paired by hydrogen bonding with its specific partner, A with T and G with C.
(b) The first step in replication is separation of the two DNA strands.
(c) Each parental strand now serves as a template that determines the order of nucleotides along a new, complementary strand.
(d) The nucleotides are connected to form the sugar-phosphate backbones of the new strands Each “daughter” DNA molecule consists of one parental strand and one new strand. A C T G T T G A C A C T G T G A C A C T G A T G A C A C T G T G A C A C T G T G A C G C A T T A C G

21. DNA Replication is “Semi-conservative”
Each 2-stranded daughter molecule is only half new
One original strand was used as a template to make the new strand

22. DNA Replication
The copying of DNA is remarkable in its speed and accuracy
Involves unwinding the double helix and synthesizing two new strands.
More than a dozen enzymes and other proteins participate in DNA replication
The replication of a DNA molecule begins at special sites called origins of replication, where the two strands are separated

23. Origins of Replication
A eukaryotic chromosome may have hundreds or even thousands of replication origins
Replication begins at specific sites
where the two parental strands
separate and form replication
bubbles.
The bubbles expand laterally, as
DNA replication proceeds in both
directions.
Eventually, the replication
bubbles fuse, and synthesis of
the daughter strands is
complete. 1 2 3
Origin of replication
Bubble
Parental (template) strand
Daughter (new) strand
Replication fork
Two daughter DNA molecules
In eukaryotes, DNA replication begins at many sites along the giant
DNA molecule of each chromosome.
In this micrograph, three replication
bubbles are visible along the DNA of
a cultured Chinese hamster cell (TEM).
(b)
(a)
0.25 µm

27. Oncogenes –
BRCA gene – breast cancer
Defect in p53 gene – colon cancer

28. Emia – means in the blood

29. X chromosome – that is why guys are more prone to color blindness or hemophilia
The sex chromosome can carry additional information
X chromosome – carrying color blindness and hemophilia
In order for a female to have color blindness they need to have both x chromosomes having color blindness trait

30. Chromosome All living organisms consist of cells.
In each cell there is chromosomes.
Chromosomes are strings of DNA
Chromosome consists
of genes, blocks of DNA.
Each gene encodes a particular protein.

31. Chromosome Each gene has its own position in the chromosome.
This position is called locus.
Complete set of genetic material (all chromosomes) is called genome.
Particular set of genes in genome is called genotype.
The genotype is with later development after birth base for the organism's phenotype, its physical and mental characteristics, such as eye color, intelligence etc.

32. DNA
DNA is a double helix composed of two intertwined nucleotide chains oriented in opposite directions.
The double helix composed of building block called nucleotides

33. DNA Each nucleotides consist : Phosphate group
Deoxyribose sugar molecule
One of four different nitrogenous bases either Purines - Adenine and Guanine, or Pyrimidines -Cytosine and Thymine)

34. DNA The functional units of DNA are genes.
A gene is a segment of DNA that can be copied to make RNA.
The nucleotide sequence in RNA is translated into the amino acid sequence of a protein.
Proteins are the main determinants of the basic structural and physiological properties of an organism.

35. Protein synthesis DNA is duplicated before a cell divides
A process called replication

36. Protein synthesis Genes are transcribed into RNA (transcription).
Genes are transcribed into RNA (transcription).
Non-coding parts are removed called mRNA
Transported out of the nucleus
Outside the nucleus, the proteins are built (translation).

37. Mutation Mutations Inherited Acquired Carrier or diseased
Caused by radiation, toxins, diet, infections

38. Mutation
Variation within a species may be from hereditary variation, environmental variation, or both.
The newly created offspring can then be mutated.
Mutation means that the elements of DNA are a bit changed.
The effect of mutation depends on both the mutation and its location

39. Mutation
Errors in the replication of DNA have been postulated as being responsible for the mutations seen in conditions such as Huntington's disease2 and myotonic dystrophy.
Errors in recombination are responsible for mutations called translocations, such as occur in leukemias and other cancers.
Normal recombination produces genetic variation by the exchange of genetic material between paired chromosomes.

40. Mutation
Mutations can arise through a variety of mechanisms range from changes in a single nucleotide to the loss, duplication or rearrangement of entire chromosomes.
When a gene contains a mutation, the protein encoded by that gene will be abnormal and sometimes changes are insignificant

41. Mutation
Some mutations are silent; they affect neither the structure of the encoded protein nor its function.
Other mutations result in an altered protein.
Certain chemicals produce DNA damage that leads to mutation, tobacco smoke, certain dyes and chemotherapeutic agents

42. Alleles Genes come in pairs, with one copy inherited from each parent.
Many genes come in a number of variant forms, known as alleles.
A dominant allele prevails over a normal allele.
A recessive gene becomes apparent if its counterpart allele on the other chromosome becomes inactivated or lost.

43. Dominant genes
In dominant genetic disorders, if one affected parent has a disease-causing allele that dominates its normal counterpart, each child in the family has a 50-percent chance of inheriting the disease allele and the disorder.

44. Recessive genes
In diseases associated with altered recessive genes, both parents - though disease-free themselves- carry one normal allele and one altered allele.
Each child has one chance in four of inheriting two altered alleles and developing the disorder;
one chance in four of inheriting two normal alleles,
two chances in four of inheriting one normal and one altered allele, and being a carrier like both parents.

45. Genetic disorders Chromosome Abnormalities
A karyotype is a display of the chromosomes of a single cell.

46. Genetic disorders Single-Gene Disorders
Some disorders due to a single gene to be altered or missing.
Example is sickle-cell anemia.
Mutations in the beta-globin gene cause blood cells to become a sickle shape.
The sickle cell easily get clogged in the narrow passages.

47. Genetic disorders Multifactorial Disorders
Multifactorial disorders result from mutations in multiple genes, often coupled with environmental causes. The complicated bases of these diseases make them difficult to study and to treat.
Heart disorder, diabetes and cancer are examples of this type of disorder.

48. What is the relationship between genes and cancer?
All cancer is genetic
It is triggered by altered genes.
A small portion of cancer is inherited
A mutation carried in reproductive cells, passed on from one generation to the next, and present in cells throughout the body.

49. What is the relationship between genes and cancer?
Most cancers come from random mutations that develop in body cells during one's lifetime - either as a mistake when cells are going through cell division or in response to injuries from environmental agents such as radiation or chemicals.

50. What is the relationship between genes and cancer?
Cancer usually arises in a single cell.
The cell's progress from normal to malignant to metastatic appears to follow a series of distinct steps, each one controlled by a different gene or set of genes.
Several types of genes have been implicated.
Oncogenes normally encourage cell growth; when mutated or overexpressed
Tumor-suppressor genes normally restrain cell growth

51. What is Genetic Testing?
Means a laboratory test of a person’s genes or chromosomes for abnormalities, defects, or deficiencies, including carrier status, that are linked to physical or mental disorders or impairments or a susceptibility to them.

52. Genetic testing How do they test? Testing for extra chromosomes
Testing of DNA
Testing for a protein

53. Genetic testing
In clinical research programs, doctors make use of genetic tests :
early detection genes prompt close surveillance for colon cancer);
diagnosis (different types of Leukaemia can be distinguished);
prognosis (the product of a mutated p53 tumour suppressor gene) flags cancers that are likely to grow aggressively); and
treatment (antibodies block a gene product that promotes the growth of breast cancer).

54. Genetic testing
Methods for detecting genetic abnormalities, depend upon the size and nature of the mutation.
Some techniques are applied to test for chromosomal DNA itself, some to the RNA copies and some to the protein product of the gene

55. Genetic testing
Single base pair mutations can be identified by any of the following methods:
Direct sequencing, which involves identifying each individual base pair, in sequence, and comparing the sequence to that of the normal gene
This tends to be a labour-intensive method reserved for previously unidentified mutations or rare mutations of a common disease (such as cystic fibrosis), when other methods do not detect the disease that is clinically suspected.

56. Genetic testing
Larger mutations involve the deletion, rearrangement, expansion or duplication of parts of genes, entire genes or multiple genes:
A number of strategies use the polymerase chain reaction to amplify specifically the region involving the mutation.

57. Genetic testing Results of genetic tests could show: Genetic diseases
Will get or already has the disease
Genetic predispositions
Could, maybe, might get the disease

58. Genetic Tests Find Mutations, NOT Disease
Women with the BRCA1 breast cancer susceptibility gene have an 80-percent chance of developing breast cancer by the age of 65.
The risk is high but not absolute
Family members who negative for the BRCA1 mutation are not exempt from breast cancer risk
over time, they can acquire breast cancer-associated genetic changes at the same rate as the general population

59. Technical Concerns
Before predictive gene tests become generally available, specialists and society must come to grips with major technical, ethical, and economic concerns.
If widespread gene testing becomes a reality, it will be necessary to develop tests that are simple, cost-effective, and accurate.

60. Technical Concerns
Testing thousands to millions of people will require many new labs and personnel as well as more genetic counselors.
Widespread gene testing will require many health care providers have a basic understanding of genetic principles in order to interpret the tests.