DNA what is it o o o Pentose

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DNA what is it o o o Pentose sugar (deoxyribose) Phosphate molecule Four nitrogenous

DNA what is it o o o Pentose sugar (deoxyribose) Phosphate molecule Four nitrogenous bases n n Pyrimidines: cytosine and thymine Purines: adenine and guanine 1 Mosby items and derived items © 2006 by Mosby, Inc.

Proteins o o One or more polypeptides Composed of amino acids n n 20

Proteins o o One or more polypeptides Composed of amino acids n n 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 2 Mosby items and derived items © 2006 by Mosby, Inc.

DNA Replication o Untwisting and unzipping of the DNA strand n o Single strand

DNA Replication o Untwisting and unzipping of the DNA strand n o Single strand acts as a template for replication and transcription to RNA Complementary base pairing done by action of DNA polymerase n Adenine-thymine; cytosine-guanine Chargraf’s rules 3 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation o Any inherited alteration of genetic material n n Chromosome aberrations major changes

Mutation o Any inherited alteration of genetic material n n Chromosome aberrations major changes in the entire DNA strand 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 o o One base pair is substituted for another Silent substitution n n 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 4 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation o Frameshift mutation n Insertion or deletion of one or more base pairs

Mutation o Frameshift mutation n Insertion or deletion of one or more base pairs Causes a change in the entire “reading frame” Examples include sickle cell anemia 5 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation 6 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation 6 Mosby items and derived items © 2006 by Mosby, Inc.

Mutation o Spontaneous mutation n o Mutation that occurs in absence of exposure to

Mutation o Spontaneous mutation n o Mutation that occurs in absence of exposure to known mutagens Mutational hotspots n Areas of the chromosomes that have high mutation rates o A cytosine base followed by a guanine are known to account for a disproportionately large percentage of disease-causing mutations 7 Mosby items and derived items © 2006 by Mosby, Inc.

Mutagen o Agent known to increase the frequency of mutations n n Radiation Chemicals

Mutagen o Agent known to increase the frequency of mutations n n Radiation Chemicals 8 Mosby items and derived items © 2006 by Mosby, Inc.

Transcription o o o RNA is synthesized from the DNA template Results in the

Transcription o o o RNA is synthesized from the DNA template Results in the formation of messenger RNA (m. RNA) m. RNA moves out of the nucleus and into the cytoplasm 9 Mosby items and derived items © 2006 by Mosby, Inc.

Transcription 10 Mosby items and derived items © 2006 by Mosby, Inc.

Transcription 10 Mosby items and derived items © 2006 by Mosby, Inc.

Translation o o Process by which RNA directs the synthesis of a polypeptide Site

Translation o o Process by which RNA directs the synthesis of a polypeptide Site of protein synthesis is the ribosome t. RNA contains a sequence of nucleotides (anticodon) complementary to the triad of nucleotides on the m. RNA strand (codon) The ribosome moves along the m. RNA sequence to translate the amino acid sequence 11 Mosby items and derived items © 2006 by Mosby, Inc.

Translation 12 Mosby items and derived items © 2006 by Mosby, Inc.

Translation 12 Mosby items and derived items © 2006 by Mosby, Inc.

Chromosomes o Somatic cells n n o Contain 46 chromosomes (23 pairs) Diploid cells

Chromosomes o Somatic cells n n o Contain 46 chromosomes (23 pairs) Diploid cells Gametes n n Contain 23 chromosomes Haploid cells o o One member of each chromosome pair Meiosis n Formation of haploid cells from diploid cells 13 Mosby items and derived items © 2006 by Mosby, Inc.

Chromosomes o Autosomes n n o The first 22 of the 23 pairs of

Chromosomes o Autosomes n n o 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 n n n Remaining pair of chromosomes In females, it is a homologous pair (XX) In males, it is a nonhomologous pair (XY) 14 Mosby items and derived items © 2006 by Mosby, Inc.

Karyotype o Ordered display of chromosomes 15 Mosby items and derived items © 2006

Karyotype o Ordered display of chromosomes 15 Mosby items and derived items © 2006 by Mosby, Inc.

Chromosome Aberrations o Euploid cells n n o When a euploid cell has more

Chromosome Aberrations o Euploid cells n n o When a euploid cell has more than the diploid number, it is called a polyploid cell n n o Cells that have a multiple of the normal number of chromosomes Haploid and diploid cells are euploid forms 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 16 Mosby items and derived items © 2006 by Mosby, Inc.

Chromosome Aberrations o Aneuploidy n n A somatic cell that does not contain a

Chromosome Aberrations o Aneuploidy n n 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 o “It is better to have extra than less” 17 Mosby items and derived items © 2006 by Mosby, Inc.

Chromosome Aberrations o Disjunction n o Normal separation of chromosomes during cell division Nondisjunction

Chromosome Aberrations o Disjunction n o Normal separation of chromosomes during cell division Nondisjunction n n Usually the cause of aneuploidy Failure of homologous chromosomes or sister chromatids to separate normally during meiosis or mitosis 18 Mosby items and derived items © 2006 by Mosby, Inc.

Nondisjunction 19 Mosby items and derived items © 2006 by Mosby, Inc.

Nondisjunction 19 Mosby items and derived items © 2006 by Mosby, Inc.

Autosomal Aneuploidy o Partial trisomy n o Only an extra portion of a chromosome

Autosomal Aneuploidy o Partial trisomy n o Only an extra portion of a chromosome is present in each cell Chromosome mosaics n Trisomies occurring only in some cells of the body 20 Mosby items and derived items © 2006 by Mosby, Inc.

Autosomal Aneuploidy o Down syndrome n Best-known example of aneuploidy o n n n

Autosomal Aneuploidy o Down syndrome n Best-known example of aneuploidy o n n n Trisomy 21 1: 800 live births Mentally retarded, low nasal bridge, epicanthal folds, protruding tongue, poor muscle tone Risk increases with maternal age 21 Mosby items and derived items © 2006 by Mosby, Inc.

Down Syndrome 22 Mosby items and derived items © 2006 by Mosby, Inc.

Down Syndrome 22 Mosby items and derived items © 2006 by Mosby, Inc.

Sex Chromosome Aneuploidy o o One of the most common is trisomy X. This

Sex Chromosome Aneuploidy o o One of the most common is trisomy X. This is a female that has three X chromosomes. Termed “metafemales” n n Symptoms are variable: sterility, menstrual irregularity, and/or mental retardation Symptoms worsen with each additional X 23 Mosby items and derived items © 2006 by Mosby, Inc.

Sex Chromosome Aneuploidy o Turner syndrome n n Females with only one X chromosome

Sex Chromosome Aneuploidy o Turner syndrome n n Females with only one X chromosome Characteristics o o o o 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 24 Mosby items and derived items © 2006 by Mosby, Inc.

Turner Syndrome 25 Mosby items and derived items © 2006 by Mosby, Inc.

Turner Syndrome 25 Mosby items and derived items © 2006 by Mosby, Inc.

Sex Chromosome Aneuploidy o Klinefelter syndrome n n Individuals with at least two Xs

Sex Chromosome Aneuploidy o Klinefelter syndrome n n Individuals with at least two Xs and one Y chromosome Characteristics o o o n 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. 26 Mosby items and derived items © 2006 by Mosby, Inc.

Klinefelter Syndrome 27 Mosby items and derived items © 2006 by Mosby, Inc.

Klinefelter Syndrome 27 Mosby items and derived items © 2006 by Mosby, Inc.

Alterations in Chromosome Structure o Chromosome breakage n n If a chromosome break does

Alterations in Chromosome Structure o Chromosome breakage n n 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 o Ionizing radiation, chemicals, and viruses 28 Mosby items and derived items © 2006 by Mosby, Inc.

Alterations in Chromosome Structure o o Breakage or loss of DNA Cri du chat

Alterations in Chromosome Structure o o Breakage or loss of DNA Cri du chat syndrome n n n “Cry of the cat” Deletion of short arm of chromosome 5 Low birth weight, metal retardation, and microcephaly 29 Mosby items and derived items © 2006 by Mosby, Inc.

Alterations in Chromosome Structure 30 Mosby items and derived items © 2006 by Mosby,

Alterations in Chromosome Structure 30 Mosby items and derived items © 2006 by Mosby, Inc.

Alterations in Chromosome Structure o Duplication n n Presence of a repeated gene or

Alterations in Chromosome Structure o Duplication n n 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 31 Mosby items and derived items © 2006 by Mosby, Inc.

Alterations in Chromosome Structure o Inversions n n n Two breaks on a chromosome

Alterations in Chromosome Structure o Inversions n n n Two breaks on a chromosome Reversal of the gene order Usually occurs from a breakage that gets reversed during reattachment o ABCDEFG may become ABEDCFG 32 Mosby items and derived items © 2006 by Mosby, Inc.

Alterations in Chromosome Structure o Translocations n n The interchanging of material between nonhomologous

Alterations in Chromosome Structure o Translocations n n The interchanging of material between nonhomologous chromosomes Translocation occurs when two chromosomes break and the segments are rejoined in an abnormal arrangement 33 Mosby items and derived items © 2006 by Mosby, Inc.

Alterations in Chromosome Structure 34 Mosby items and derived items © 2006 by Mosby,

Alterations in Chromosome Structure 34 Mosby items and derived items © 2006 by Mosby, Inc.

Alterations in Chromosome Structure 35 Mosby items and derived items © 2006 by Mosby,

Alterations in Chromosome Structure 35 Mosby items and derived items © 2006 by Mosby, Inc.

Alterations in Chromosome Structure o Fragile sites n n Fragile sites areas on chromosomes

Alterations in Chromosome Structure o Fragile sites n n Fragile sites areas on chromosomes that develop distinctive breaks or gaps when cells are cultured No apparent relationship to disease 36 Mosby items and derived items © 2006 by Mosby, Inc.

Alterations in Chromosome Structure o Fragile X syndrome n n n Site on the

Alterations in Chromosome Structure o Fragile X syndrome n n n 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 37 Mosby items and derived items © 2006 by Mosby, Inc.

Genetics o Gregor Mendel n n n Austrian monk Garden pea experiments Mendelian traits

Genetics o Gregor Mendel n n n Austrian monk Garden pea experiments Mendelian traits 38 Mosby items and derived items © 2006 by Mosby, Inc.

Genetics o Locus n o Position of a gene along a chromosome Allele n

Genetics o Locus n o Position of a gene along a chromosome Allele n n n A different form of a particular gene at a given locus Example: Hgb A vs. Hgb S Polymorphism o Locus that has two or more alleles that occur with appreciable frequency 39 Mosby items and derived items © 2006 by Mosby, Inc.

Genetics o Homozygous n n Loci on a pair of chromosomes have identical genes

Genetics o Homozygous n n Loci on a pair of chromosomes have identical genes Example o o O blood type (OO) Heterozygous n n Loci on a pair of chromosomes have different genes Example o AB blood type (A and B genes on pair of loci) 40 Mosby items and derived items © 2006 by Mosby, Inc.

Genetics o Genotype (“what they have”) n o Phenotype (“what they demonstrate”) n o

Genetics o Genotype (“what they have”) n o Phenotype (“what they demonstrate”) n o The genetic makeup of an organism The observable, detectable, or outward appearance of the genetics of an organism Example n A person with the A blood type could be AA or AO. A is the phenotype; AA or AO would be the genotype. 41 Mosby items and derived items © 2006 by Mosby, Inc.

Genetics o o o If two alleles are found together, the allele that is

Genetics o o o 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 42 Mosby items and derived items © 2006 by Mosby, Inc.

Genetics o Carrier n n n A carrier is one that has a disease

Genetics o Carrier n n n 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 o o Ss = sickle cell anemia carrier ss = demonstrates sickle cell disease 43 Mosby items and derived items © 2006 by Mosby, Inc.

Pedigrees o o Used to study specific genetic disorders within families Begins with the

Pedigrees o o Used to study specific genetic disorders within families Begins with the proband 44 Mosby items and derived items © 2006 by Mosby, Inc.

Pedigrees 45 Mosby items and derived items © 2006 by Mosby, Inc.

Pedigrees 45 Mosby items and derived items © 2006 by Mosby, Inc.

Single-Gene Disorders o Recurrence risk n n The probability that parents of a child

Single-Gene Disorders o Recurrence risk n n 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 o 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 46 Mosby items and derived items © 2006 by Mosby, Inc.

Single-Gene Disorders o Autosomal dominant disorder n Abnormal allele is dominant, normal allele is

Single-Gene Disorders o Autosomal dominant disorder n Abnormal allele is dominant, normal allele is recessive, and the genes exist on a pair of autosomes 47 Mosby items and derived items © 2006 by Mosby, Inc.

Single-Gene Disorders o Autosomal dominant traits 48 Mosby items and derived items © 2006

Single-Gene Disorders o Autosomal dominant traits 48 Mosby items and derived items © 2006 by Mosby, Inc.

Single-Gene Disorders o Autosomal dominant trait pedigree 49 Mosby items and derived items ©

Single-Gene Disorders o Autosomal dominant trait pedigree 49 Mosby items and derived items © 2006 by Mosby, Inc.

Penetrance o The percentage of individuals with a specific genotype who also express the

Penetrance o The percentage of individuals with a specific genotype who also express the expected phenotype n Incomplete penetrance o o Individual who has the gene for a disease but does not express the disease Retinoblastoma (eye tumor in children) demonstrates incomplete penetrance (90%) 50 Mosby items and derived items © 2006 by Mosby, Inc.

Expressivity o o o Expressivity is the variation in a phenotype associated with a

Expressivity o o o Expressivity is the variation in a phenotype associated with a particular genotype This can be caused by modifier genes Examples: n n 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. 51 Mosby items and derived items © 2006 by Mosby, Inc.

Expressivity 52 Mosby items and derived items © 2006 by Mosby, Inc.

Expressivity 52 Mosby items and derived items © 2006 by Mosby, Inc.

Single-Gene Disorders o Autosomal recessive disorder n n Abnormal allele is recessive and a

Single-Gene Disorders o Autosomal recessive disorder n n 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 53 Mosby items and derived items © 2006 by Mosby, Inc.

Single-Gene Disorders o Autosomal recessive disorder recurrence risk n Recurrence risk of an autosomal

Single-Gene Disorders o Autosomal recessive disorder recurrence risk n Recurrence risk of an autosomal dominant trait o When two parents are carriers of an autosomal recessive disease, the occurrence and recurrence risks for each child are 25% 54 Mosby items and derived items © 2006 by Mosby, Inc.

Autosomal Recessive Disorder 55 Mosby items and derived items © 2006 by Mosby, Inc.

Autosomal Recessive Disorder 55 Mosby items and derived items © 2006 by Mosby, Inc.

Consanguinity o o Mating of two related individuals Dramatically increases the recurrence risk of

Consanguinity o o Mating of two related individuals Dramatically increases the recurrence risk of recessive disorders 56 Mosby items and derived items © 2006 by Mosby, Inc.

Sex-Linked Disorders o The Y chromosome contains only a few dozen genes, so most

Sex-Linked Disorders o 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 57 Mosby items and derived items © 2006 by Mosby, Inc.

Sex-Linked Disorders o o Sex-linked (X-linked) disorders are usually expressed by males because females

Sex-Linked Disorders o o Sex-linked (X-linked) disorders are usually expressed by males because females have another X chromosome to mask the abnormal gene X-linked recessive n n n 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 Mosby items and derived items © 2006 by Mosby, Inc. 58

Sex-Linked Disorders 59 Mosby items and derived items © 2006 by Mosby, Inc.

Sex-Linked Disorders 59 Mosby items and derived items © 2006 by Mosby, Inc.

Gene Mapping 60 Mosby items and derived items © 2006 by Mosby, Inc.

Gene Mapping 60 Mosby items and derived items © 2006 by Mosby, Inc.