Mosby items and derived items © 2006 by Mosby, Inc. 1 DNA what is it Pentose sugar (deoxyribose) ...

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

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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 Chargraf’s

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 don’t 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

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 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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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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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

Mosby items and derived items © 2006 by Mosby, Inc. 1 DNA what is it Pentose sugar (deoxyribose) ...

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