DNA what is it

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DNA what is it

• Pentose sugar (deoxyribose)
• Phosphate molecule
• Four nitrogenous bases
• Pyrimidines cytosine and thymine
• Purines adenine and guanine

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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

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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 Chargrafs rules

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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

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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

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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
• 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

• 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

• Somatic cells
• 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

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Chromosomes

• Autosomes
• 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)

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Karyotype

• Ordered display of chromosomes

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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 dont survive

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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

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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

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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
• Best-known example of aneuploidy
• Trisomy 21
• 1800 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

• 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

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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

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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
• 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.

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Klinefelter Syndrome
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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

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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

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Alterations in Chromosome Structure
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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

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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

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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

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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
• 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
• 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
• Austrian monk
• Garden pea experiments
• Mendelian traits

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Genetics

• Locus
• Position of a gene along a chromosome
• Allele
• 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

• Homozygous
• Loci on a pair of chromosomes have identical
  genes
• Example
• O blood type (OO)
• Heterozygous
• 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

• 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
• 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

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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
• 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
• 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

• 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.

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Expressivity
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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

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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

• 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

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Sex-Linked Disorders
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Gene Mapping