Review and Alterations

Terminology
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Chromosome: types, number
Haploid, Diploid
Gene, Allele, Loci
Homozygous, Heterozygous
Karyotype, Phenotype, Genotype
Carrier, Dominant, Recessive
Nucleic Acids, Base Pairs
Replication: DNA, mitosis, meiosis
Protein Synthesis
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Transcription
Translation

Chromosome Pairs in Species

Chromosome Types

Chromosome #: Long to Short

Human Karyotype

Chromosome Arms and Centromere

Homologous Chromosomes

Allele and Loci

Homozygous and Heterozygous

Phenotype and Genotype

Carrier, Dominant, Recessive

Chromosome structure

Chromosome vs Chromatin

Looped Domains and Chromatin

Histones and Nucleosomes

DNA

DNA structure

Gene
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1.5% of Genome
DNA base pairs
(~ 100,000)
Encode a product
(protein, tRNA, rRNA)
Responsible for a measurable trait
Introns
Exons

DNA Base Pairs

Nucleoside

DNA Replication

Cell Cycle Review

Mitosis

Meiosis

Mitosis and Meiosis Compared

Meiosis I: Normal

Non Disjunction

Chromosome Disorders
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Chromosome Number
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Euploid (2N)
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Polyploid (exact multiple)
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Triplody (3N)
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Tetraplody (4N)
Anueploid (not exact multiple)
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Trisomic (n + 1)
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Autosomes
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Down’s Syndrome
Sex Chromosomes
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Klinefelter
Monosomic (n-1)
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Sex Chromosome
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Turner
Mosaics (not all cells affected)
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Somatic
Gonadal

Anaphase

Extra Chromosomal Disorders

Down Syndrome (Trisomy 21)

Anueploid

Chromosome Abnormalities
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Structure
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Break and reassemble abnormally
Inversion
Translocation
Insertion
Deletion
Duplication

Inversions

Translocations

Translocation in Meiosis

Insertions and Deletions

Insertion

Deletion
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1, 2, or 3 base pairs are deleted
Frameshift reading

Chromosome Deletions

Deletion example

Prader-Willi / Angelman Syndromes

Cancers caused by Deletions

Wilms Tumor

Duplications
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Doubling section of genome
Unequal Crossing over
Multiple repeats of nucleotides

DNA section duplicated
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Huntington’s
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CAG repeated
Fragile X
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CGG repeated
MD
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CTG repeated

Chromosomal Mutation Summary

DNA Transcription

Transcription Steps

Translation

DNA codon for AA

DNA Damage

Mutation:
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Define
S phase
Types
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Single Base Pair substitution
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Missense
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Nonsense
Silent
Frame shift
Spontaneous
Induced

Base Pair Substitution (point mutation)
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Transition
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Purine for Purine
Pyrimadine for
Pyrimadine
Transversion
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Purine for
Pyrimadine
Pyrimadine for
Purine

Transition

Nonsense Mutation
Transversion: UGC to UGA
Nonsense mutations result in stop codons

Nonsense Mutations
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Codon changed
Stop codon is read
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TAA
TAG
TGA

Missense Mutation
Transversion: UGC to UGG

Missense Mutation
Miscoding of AA can lead to diseases such as SSA and CF

Silent Mutation

Frame Shift

Mutation Summary

Spontaneous Mutations
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Depurination
Deamination
Oxidation damage to DNA

Spontaneous Mutations in the population

Depurination and Deamination
Depurination
Deamination

Induced Mutations
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Mutagentic Base
Analog
Chemical Agents
Ultraviolet
Radiation
Ionizing Radiation

Induced Mutations
Base Analog Mutagen
UV

Ionizing Radiation

Mendelian Inheritance Patterns
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Dominant /
Recessive
CoDominance
Incomplete
Dominance
Sex Linked
Multifactoral

Dominant, Recessive, Sex-linked

Sex-Linked Punnett Square

CoDominance: Blood Types

Incomplete Dominance: SSA

Incomplete Dominance: OI

Genetic Disorders: Single Gene
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Autosomal
Dominant
Autosomal
Recessive
X-linked dominant
X-linked recessive

Hereditary Map of Autosomal Dominant Traits

Autosomal Dominant
Achondroplastic dwarfism vonWillibrand’s Disease
Neurofibromatosis
Polycystic Kidney Disease
Alzheimers (10% of cases)
Machado-Joseph
Marfan syndrome
Abnormal endochondrial bone formation causing dwarfism
Factor VIII defect causing bleeding disorders
Increased neurofibromatoma
Cystic enlargement, hematuria, hypertension, and possible renal failure dementia
Spinocerebellar degeneration
Abnormal fibrillin causing excessive bone growth, ocular disorders, & cardiac defects

Huntington Disease
Basal ganglia

Huntington brain compared to normal

Hydrocephalus

Hydrocephalus brain image

Polycystic Kidney Disease

PKD
Cat kidney
Human kidney

Neurofibromatosis

Neurofibromatosis
Clinical Signs

Marfan Syndrome
Abnormal fibrillin,
Affects elastic C.T.

Osteogenesis Imperfecta

Autosomal Dominant: Metabolic
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Familial hypercholesterolemia
Acute intermittent porphyria

Familial Hypercholesterolemia

Polydactylia

Autosomal Dominant Gene Therapy

Autosomal Recessive
Albinism
Sickle Cell Anemia
Tyrosine can not be changed to melanin for pigment
Amino acid substitution in beta chain of hemoglobin, sickling

X and Y Chromosomes

X-linked Disease Pedigree

Sex-Linked

Sex Linked
Disease
DMD (Xp21)
Menkes (Xq12-q13)
Color Blindness
Hemophilia A (Xq28)
Fabry (X
SCID (Xq13.1)
Symptoms
Muscular weakness and degeneration due to lack of dystrophin protein
Copper storage disease that leads to neurodegeneration and CT disorders
Defective function of cones for red and green color vision
Bleeding disorder due to a Factor VIII deficiency
Temperature intolerance, enlarged heart, whole body pain, depression, vomiting / diarrhea
Immune deficiency impairment, death

X-linked Diseases

Hemophilia

Duchenne Muscular Dystrophy
Absence of Dystrophin causes membrane to leak CP causing weakness associated with DMD

X-Linked SCID Inheritance
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Most common form
Mutation in IL-2 receptor gene
Lymphopenia
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Absence of T cells
Absence of NK cells
Abnormal B cells

Other X-linked Immune Diseases

Loci on X and Y Chromosomes

Fun Y Chromosome loci

Multifactoral Inheritance
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Several Genes
Environmental factors
Cluster in families
Examples
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Cleft lip or palate
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Congenital heart disease
Club foot
Pyloric Stenosis

Multifactoral

Gene Map of Disease Loci

Chromosome 4 Conditions

Epigenetic Alterations
Methylated DNA is inactivated

Gene Expression

Cell Cycle

Mitochondria

Mitochondrial DNA (mtDNA)

Chromosomes in Mitochondria
Heavy Strand
Light Strand

DNA compared

Inheritance Patterns Compared

Results of Inheritance Patterns

Mitochondrial DNA disorders

Mitochondrial Genetic Diseases

Additional Terminology
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Congenital Defect
Mutagen
Teratogen
Carcinogen
Hot Spots
Cloning

Genetic Testing

Karyotyping of Sample

Genetic Counseling

Gene Therapy

Questions?