DNA what is it
 Pentose sugar (deoxyribose)
 Phosphate molecule
 Four nitrogenous bases
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Pyrimidines: cytosine and thymine
Purines: adenine and guanine
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Proteins
 One or more polypeptides
 Composed of amino acids
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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
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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
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Mutation
 Any inherited alteration of genetic material
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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
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One base pair is substituted for another
Silent substitution
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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
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Mutation
 Frameshift mutation
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Insertion or deletion of one or more base pairs
Causes a change in the entire “reading frame”
Examples include sickle cell anemia
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Mutation
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Mutation
 Spontaneous mutation
 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
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Mutagen
 Agent known to increase the frequency of mutations
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Radiation
Chemicals
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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
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Transcription
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Translation
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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
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Translation
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Chromosomes
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Somatic cells
 Contain 46 chromosomes (23 pairs)
 Diploid cells
Gametes
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Contain 23 chromosomes
Haploid cells
 One member of each chromosome pair
Meiosis
 Formation of haploid cells from diploid cells
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Chromosomes
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Autosomes
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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
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Remaining pair of chromosomes
In females, it is a homologous pair (XX)
In males, it is a nonhomologous pair (XY)
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Karyotype
 Ordered display of chromosomes
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Chromosome Aberrations
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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
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Chromosome Aberrations
 Aneuploidy
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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
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“It is better to have extra than less”
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Chromosome Aberrations
 Disjunction
 Normal separation of chromosomes during cell division
 Nondisjunction
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Usually the cause of aneuploidy
Failure of homologous chromosomes or sister chromatids to separate normally during meiosis or mitosis
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Nondisjunction
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Autosomal Aneuploidy
 Partial trisomy
 Only an extra portion of a chromosome is present in each cell
 Chromosome mosaics
 Trisomies occurring only in some cells of the body
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Autosomal Aneuploidy
 Down syndrome
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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
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Down Syndrome
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Sex Chromosome Aneuploidy
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One of the most common is trisomy X. This is a female that has three X chromosomes.
Termed “metafemales”
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Symptoms are variable: sterility, menstrual irregularity, and/or mental retardation
Symptoms worsen with each additional X
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Sex Chromosome Aneuploidy
 Turner syndrome
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Females with only one X chromosome
Characteristics
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Absence of ovaries (sterile)
Short stature (~ 4'7")
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Webbing of the neck
Edema
Underdeveloped breasts; wide nipples
High number of aborted fetuses
X is usually inherited from mother
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Turner Syndrome
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Sex Chromosome Aneuploidy
 Klinefelter syndrome
 Individuals with at least two Xs and one Y chromosome
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Characteristics
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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.
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Klinefelter Syndrome
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Alterations in Chromosome
Structure
 Chromosome breakage
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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
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Alterations in Chromosome
Structure
 Breakage or loss of DNA
 Cri du chat syndrome
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“Cry of the cat”
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Deletion of short arm of chromosome 5
Low birth weight, metal retardation, and microcephaly
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Alterations in Chromosome
Structure
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Alterations in Chromosome
Structure
 Duplication
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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
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Alterations in Chromosome
Structure
 Inversions
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Two breaks on a chromosome
Reversal of the gene order
Usually occurs from a breakage that gets reversed during reattachment
 ABCDEFG may become AB EDC FG
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Alterations in Chromosome
Structure
 Translocations
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The interchanging of material between nonhomologous chromosomes
Translocation occurs when two chromosomes break and the segments are rejoined in an abnormal arrangement
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Alterations in Chromosome
Structure
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Alterations in Chromosome
Structure
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Alterations in Chromosome
Structure
 Fragile sites
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Fragile sites are areas on chromosomes that develop distinctive breaks or gaps when cells are cultured
No apparent relationship to disease
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Alterations in Chromosome
Structure
 Fragile X syndrome
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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
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Genetics
 Gregor Mendel
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Austrian monk
Garden pea experiments
Mendelian traits
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Genetics
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Locus
 Position of a gene along a chromosome
Allele
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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
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Genetics
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Homozygous
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Loci on a pair of chromosomes have identical genes
Example
 O blood type (OO)
Heterozygous
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Loci on a pair of chromosomes have different genes
Example
 AB blood type (A and B genes on pair of loci)
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Genetics
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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.
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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
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Genetics
 Carrier
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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
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Ss = sickle cell anemia carrier ss = demonstrates sickle cell disease
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Pedigrees
 Used to study specific genetic disorders within families
 Begins with the proband
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Pedigrees
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Single-Gene Disorders
 Recurrence risk
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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
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Single-Gene Disorders
 Autosomal dominant disorder
 Abnormal allele is dominant, normal allele is recessive, and the genes exist on a pair of autosomes
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Single-Gene Disorders
 Autosomal dominant traits
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Single-Gene Disorders
 Autosomal dominant trait pedigree
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Penetrance
 The percentage of individuals with a specific genotype who also express the expected phenotype
 Incomplete penetrance
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Individual who has the gene for a disease but does not express the disease
Retinoblastoma (eye tumor in children) demonstrates incomplete penetrance (90%)
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Expressivity
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 Expressivity is the variation in a phenotype associated with a particular genotype
This can be caused by modifier genes
Examples:
 von Recklinghausen disease
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Autosomal dominant
Long arm of chromosome #17
Disease varies from dark spots on the skin to malignant neurofibromas, scoliosis, gliomas, neuromas, etc.
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Expressivity
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Single-Gene Disorders
 Autosomal recessive disorder
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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
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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%
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Autosomal Recessive Disorder
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Consanguinity
 Mating of two related individuals
 Dramatically increases the recurrence risk of recessive disorders
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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
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Sex-Linked Disorders
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Sex-linked (X-linked) disorders are usually expressed by males because females have another X chromosome to mask the abnormal gene
X-linked recessive
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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
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Sex-Linked Disorders
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Gene Mapping
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