1. DNA what is it Pentose sugar (deoxyribose) Phosphate molecule
Four nitrogenous bases
Pyrimidines: cytosine and thymine
Purines: adenine and guanine

2. Proteins One or more polypeptides Composed of amino acids
20 amino acids of 64 total known are found in the structure of all plants and animals 6 we can not manufacture from scratch and are essential in diet
Directed by sequence of bases along DNA strans 3 consecutive bases = a codon

3. DNA Replication Untwisting and unzipping of the DNA strand
Single strand acts as a template for replication and transcription to RNA
Complementary base pairing done by action of DNA polymerase
Adenine-thymine; cytosine-guanine Chargraf’s rules

4. Mutation Any inherited alteration of genetic material
Chromosome aberrations major changes in the entire DNA strand and entire piece missing or an extra chromosome or even an extra complete set examples include Cri – du – chat mising piece of #5 or trisomy 21 Downs syndrome extra 21 chromosome
Base pair substitution
One base pair is substituted for another
Silent substitution
Substitution that does not result in an amino acid change because genetic code is redundant
RNA codons GUU, GUC, GUA, GUG all code for the amino acid valine

5. Mutation Frameshift mutation
Insertion or deletion of one or more base pairs
Causes a change in the entire “reading frame”
Examples include sickle cell anemia

6. Mutation

7. Mutation Spontaneous mutation Mutational hotspots
Mutation that occurs in absence of exposure to known mutagens
Mutational hotspots
Areas of the chromosomes that have high mutation rates
A cytosine base followed by a guanine are known to account for a disproportionately large percentage of disease-causing mutations

8. Mutagen Agent known to increase the frequency of mutations Radiation
Chemicals

9. Transcription RNA is synthesized from the DNA template
Results in the formation of messenger RNA (mRNA)
mRNA moves out of the nucleus and into the cytoplasm

10. Transcription

11. Translation
Process by which RNA directs the synthesis of a polypeptide
Site of protein synthesis is the ribosome
tRNA contains a sequence of nucleotides (anticodon) complementary to the triad of nucleotides on the mRNA strand (codon)
The ribosome moves along the mRNA sequence to translate the amino acid sequence

12. Translation

13. Chromosomes Somatic cells Gametes Meiosis
Contain 46 chromosomes (23 pairs)
Diploid cells
Gametes
Contain 23 chromosomes
Haploid cells
One member of each chromosome pair
Meiosis
Formation of haploid cells from diploid cells

14. Chromosomes Autosomes Sex chromosomes
The first 22 of the 23 pairs of chromosomes in males and females
The two members are virtually identical and thus said to be homologous
Sex chromosomes
Remaining pair of chromosomes
In females, it is a homologous pair (XX)
In males, it is a nonhomologous pair (XY)

15. Karyotype
Ordered display of chromosomes

16. Chromosome Aberrations
Euploid cells
Cells that have a multiple of the normal number of chromosomes
Haploid and diploid cells are euploid forms
When a euploid cell has more than the diploid number, it is called a polyploid cell
Triploidy: a zygote having three copies of each chromosome (69)
Tetraploidy: four copies of each (92 total)
Both triploid and tetraploid fetuses don’t survive

17. Chromosome Aberrations
Aneuploidy
A somatic cell that does not contain a multiple of 23 chromosomes
A cell containing three copies of one chromosome is trisomic (trisomy)
Monosomy is the presence of only one copy of any chromosome
Monosomy is often lethal, but infants can survive with trisomy of certain chromosomes
“It is better to have extra than less”

18. Chromosome Aberrations
Disjunction
Normal separation of chromosomes during cell division
Nondisjunction
Usually the cause of aneuploidy
Failure of homologous chromosomes or sister chromatids to separate normally during meiosis or mitosis

19. Nondisjunction

20. Autosomal Aneuploidy Partial trisomy Chromosome mosaics
Only an extra portion of a chromosome is present in each cell
Chromosome mosaics
Trisomies occurring only in some cells of the body

21. Autosomal Aneuploidy Down syndrome Best-known example of aneuploidy
Trisomy 21
1:800 live births
Mentally retarded, low nasal bridge, epicanthal folds, protruding tongue, poor muscle tone
Risk increases with maternal age

22. Down Syndrome

23. Sex Chromosome Aneuploidy
One of the most common is trisomy X. This is a female that has three X chromosomes.
Termed “metafemales”
Symptoms are variable: sterility, menstrual irregularity, and/or mental retardation
Symptoms worsen with each additional X

24. Sex Chromosome Aneuploidy
Turner syndrome
Females with only one X chromosome
Characteristics
Absence of ovaries (sterile)
Short stature (~ 4'7")
Webbing of the neck
Edema
Underdeveloped breasts; wide nipples
High number of aborted fetuses
X is usually inherited from mother

25. Turner Syndrome

26. Sex Chromosome Aneuploidy
Klinefelter syndrome
Individuals with at least two Xs and one Y chromosome
Characteristics
Male appearance
Develop female-like breasts
Small testes
Sparse body hair
Long limbs
Some individuals can be XXXY and XXXXY. The abnormalities will increase with each X.

27. Klinefelter Syndrome

28. Alterations in Chromosome Structure
Chromosome breakage
If a chromosome break does occur, physiological mechanisms will usually repair the break, but the breaks often heal in a way that alters the structure of the chromosome
Agents of chromosome breakage
Ionizing radiation, chemicals, and viruses

29. Alterations in Chromosome Structure
Breakage or loss of DNA
Cri du chat syndrome
“Cry of the cat”
Deletion of short arm of chromosome 5
Low birth weight, metal retardation, and microcephaly

30. Alterations in Chromosome Structure

31. Alterations in Chromosome Structure
Duplication
Presence of a repeated gene or gene sequence
Rare occurrence
Less serious consequences because better to have more genetic material than less (deletion)
Duplication in the same region as cri du chat causes mental retardation but no physical abnormalities

32. Alterations in Chromosome Structure
Inversions
Two breaks on a chromosome
Reversal of the gene order
Usually occurs from a breakage that gets reversed during reattachment
ABCDEFG may become ABEDCFG

33. Alterations in Chromosome Structure
Translocations
The interchanging of material between nonhomologous chromosomes
Translocation occurs when two chromosomes break and the segments are rejoined in an abnormal arrangement

34. Alterations in Chromosome Structure

35. Alterations in Chromosome Structure

36. Alterations in Chromosome Structure
Fragile sites
Fragile sites are areas on chromosomes that develop distinctive breaks or gaps when cells are cultured
No apparent relationship to disease

37. Alterations in Chromosome Structure
Fragile X syndrome
Site on the long arm of the X chromosome
Associated with mental retardation; second in occurrence to Down syndrome
Higher incidence in males because they have only one X chromosome

38. Genetics Gregor Mendel Austrian monk Garden pea experiments
Mendelian traits

39. Genetics Locus Allele Position of a gene along a chromosome
A different form of a particular gene at a given locus
Example: Hgb A vs. Hgb S
Polymorphism
Locus that has two or more alleles that occur with appreciable frequency

40. Genetics Homozygous Heterozygous
Loci on a pair of chromosomes have identical genes
Example
O blood type (OO)
Heterozygous
Loci on a pair of chromosomes have different genes
AB blood type (A and B genes on pair of loci)

41. Genetics Genotype (“what they have”)
The genetic makeup of an organism
Phenotype (“what they demonstrate”)
The observable, detectable, or outward appearance of the genetics of an organism
Example
A person with the A blood type could be AA or AO. A is the phenotype; AA or AO would be the genotype.

42. Genetics
If two alleles are found together, the allele that is observable is dominant, and the one whose effects are hidden is recessive
In genetics, the dominant allele is represented by a capital letter, and the recessive by a lowercase letter
Alleles can be co-dominant

43. Genetics
Carrier
A carrier is one that has a disease gene but is phenotypically normal
For a person to demonstrate a recessive disease, the pair of recessive genes must be inherited
Example
Ss = sickle cell anemia carrier
ss = demonstrates sickle cell disease

44. Pedigrees Used to study specific genetic disorders within families
Begins with the proband

45. Pedigrees

46. Single-Gene Disorders
Recurrence risk
The probability that parents of a child with a genetic disease will have yet another child with the same disease
Recurrence risk of an autosomal dominant trait
When one parent is affected by an autosomal dominant disease and the other is normal, the occurrence and recurrence risks for each child are one half

47. Single-Gene Disorders
Autosomal dominant disorder
Abnormal allele is dominant, normal allele is recessive, and the genes exist on a pair of autosomes

48. Single-Gene Disorders
Autosomal dominant traits

49. Single-Gene Disorders
Autosomal dominant trait pedigree

50. Penetrance
The percentage of individuals with a specific genotype who also express the expected phenotype
Incomplete penetrance
Individual who has the gene for a disease but does not express the disease
Retinoblastoma (eye tumor in children) demonstrates incomplete penetrance (90%)

51. Expressivity
Expressivity is the variation in a phenotype associated with a particular genotype
This can be caused by modifier genes
Examples:
von Recklinghausen disease
Autosomal dominant
Long arm of chromosome #17
Disease varies from dark spots on the skin to malignant neurofibromas, scoliosis, gliomas, neuromas, etc.

52. Expressivity

53. Single-Gene Disorders
Autosomal recessive disorder
Abnormal allele is recessive and a person must be homozygous for the abnormal trait to express the disease
The trait usually appears in the children, not the parents, and it affects the genders equally because it is present on a pair of autosomes

54. Single-Gene Disorders
Autosomal recessive disorder recurrence risk
Recurrence risk of an autosomal dominant trait
When two parents are carriers of an autosomal recessive disease, the occurrence and recurrence risks for each child are 25%

55. Autosomal Recessive Disorder

56. Consanguinity Mating of two related individuals
Dramatically increases the recurrence risk of recessive disorders

57. Sex-Linked Disorders
The Y chromosome contains only a few dozen genes, so most sex-linked traits are located on the X chromosome and are said to be X-linked

58. Sex-Linked Disorders
Sex-linked (X-linked) disorders are usually expressed by males because females have another X chromosome to mask the abnormal gene
X-linked recessive
Most X-linked disorders are recessive
Affected males cannot transmit the genes to sons, but they can to all daughters
Sons of female carriers have a 50% risk of being affected

59. Sex-Linked Disorders

60. Gene Mapping