Review and Alterations Genetics Review and Alterations

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

Anaphase

Extra Chromosomal Disorders

Down Syndrome (Trisomy 21)

Anueploid

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

Inversions

Translocations

Translocation in Meiosis

Insertions and Deletions

Insertion

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

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

Chromosomal Mutation Summary

DNA Transcription

Transcription Steps

Translation

DNA codon for AA

DNA Damage

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

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

Transition

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

Nonsense Mutations Codon changed Stop codon is read 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 Depurination Deamination Oxidation damage to DNA

Spontaneous Mutations in the population

Depurination and Deamination

Induced Mutations Mutagentic Base Analog Chemical Agents Ultraviolet Radiation Ionizing Radiation

Induced Mutations UV Base Analog Mutagen

Ionizing Radiation

Mendelian Inheritance Patterns 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 Autosomal Dominant Autosomal Recessive X-linked dominant X-linked recessive

Hereditary Map of Autosomal Dominant Traits

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

Neurofibromatosis

Neurofibromatosis Clinical Signs

Marfan Syndrome Abnormal fibrillin, Affects elastic C.T.

Osteogenesis Imperfecta

Autosomal Dominant: Metabolic 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 Sickle Cell Anemia Amino acid substitution in beta chain of hemoglobin, sickling

X and Y Chromosomes

X-linked Disease Pedigree

Sex-Linked

Sex Linked Disease Symptoms DMD (Xp21) Menkes (Xq12-q13) Muscular weakness and degeneration due to lack of dystrophin protein Menkes (Xq12-q13) Copper storage disease that leads to neurodegeneration and CT disorders Color Blindness Defective function of cones for red and green color vision Hemophilia A (Xq28) Bleeding disorder due to a Factor VIII deficiency Fabry (X Temperature intolerance, enlarged heart, whole body pain, depression, vomiting / diarrhea SCID (Xq13.1) 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 Most common form Mutation in IL-2 receptor gene Lymphopenia 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 Several Genes Environmental factors Cluster in families Examples Cleft lip or palate 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 Congenital Defect Mutagen Teratogen Carcinogen Hot Spots Cloning

Genetic Testing

Karyotyping of Sample

Genetic Counseling

Gene Therapy

Questions?