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DNA what is it
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Pentose sugar (deoxyribose)
Phosphate molecule
Four nitrogenous bases
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Pyrimidines: cytosine and thymine
Purines: adenine and guanine
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Proteins
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One or more polypeptides
Composed of amino acids
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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
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Untwisting and unzipping of the DNA
strand
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Single strand acts as a template for replication
and transcription to RNA
Complementary base pairing done by action
of DNA polymerase
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Adenine-thymine; cytosine-guanine Chargraf’s
rules
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Mutation
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Any inherited alteration of genetic material
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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
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One base pair is substituted for another
Silent substitution
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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
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Frameshift mutation
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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
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Spontaneous mutation
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Mutation that occurs in absence of exposure to
known mutagens
Mutational hotspots
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Areas of the chromosomes that have high
mutation rates
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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
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Agent known to increase the frequency of
mutations
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Radiation
Chemicals
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Transcription
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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
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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
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Somatic cells
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Contain 46 chromosomes (23 pairs)
Diploid cells
Gametes
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Contain 23 chromosomes
Haploid cells
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One member of each chromosome pair
Meiosis
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Formation of haploid cells from diploid cells
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Chromosomes
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Autosomes
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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
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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
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Ordered display of chromosomes
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Chromosome Aberrations
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Euploid cells
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When a euploid cell has more than the diploid
number, it is called a polyploid cell
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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
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Chromosome Aberrations
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Aneuploidy
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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
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“It is better to have extra than less”
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Chromosome Aberrations
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Disjunction
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Normal separation of chromosomes during cell
division
Nondisjunction
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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
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Partial trisomy
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Only an extra portion of a chromosome is
present in each cell
Chromosome mosaics
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Trisomies occurring only in some cells of the
body
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Autosomal Aneuploidy
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Down syndrome
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Best-known example of aneuploidy
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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
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One of the most common is trisomy X. This
is a female that has three X chromosomes.
Termed “metafemales”
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Symptoms are variable: sterility, menstrual
irregularity, and/or mental retardation
Symptoms worsen with each additional X
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Sex Chromosome Aneuploidy
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Turner syndrome
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Females with only one X chromosome
Characteristics
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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
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Klinefelter syndrome
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Individuals with at least two Xs and one Y chromosome
Characteristics
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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
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Chromosome breakage
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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
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Ionizing radiation, chemicals, and viruses
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Alterations in Chromosome
Structure
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Breakage or loss of DNA
Cri du chat syndrome
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“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
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Duplication
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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
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Inversions
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Two breaks on a chromosome
Reversal of the gene order
Usually occurs from a breakage that gets
reversed during reattachment
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ABCDEFG may become ABEDCFG
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Alterations in Chromosome
Structure
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Translocations
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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
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Fragile sites
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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
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Fragile X syndrome
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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
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Gregor Mendel
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Austrian monk
Garden pea experiments
Mendelian traits
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Genetics
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Locus
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Position of a gene along a chromosome
Allele
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A different form of a particular gene at a given
locus
Example: Hgb A vs. Hgb S
Polymorphism
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Locus that has two or more alleles that occur with
appreciable frequency
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Genetics
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Homozygous
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Loci on a pair of chromosomes have identical
genes
Example
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O blood type (OO)
Heterozygous
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Loci on a pair of chromosomes have different
genes
Example
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AB blood type (A and B genes on pair of loci)
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Genetics
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Genotype (“what they have”)
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Phenotype (“what they demonstrate”)
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The genetic makeup of an organism
The observable, detectable, or outward
appearance of the genetics of an organism
Example
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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
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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
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Carrier
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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
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Ss = sickle cell anemia carrier
ss = demonstrates sickle cell disease
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Pedigrees
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Used to study specific genetic disorders
within families
Begins with the proband
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Pedigrees
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Single-Gene Disorders
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Recurrence risk
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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
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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
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Autosomal dominant disorder
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Abnormal allele is dominant, normal allele is
recessive, and the genes exist on a pair of
autosomes
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Single-Gene Disorders
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Autosomal dominant traits
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Single-Gene Disorders
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Autosomal dominant trait pedigree
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Penetrance
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The percentage of individuals with a
specific genotype who also express the
expected phenotype
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Incomplete penetrance
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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
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Expressivity is the variation in a phenotype
associated with a particular genotype
This can be caused by modifier genes
Examples:
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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
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Autosomal recessive disorder
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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
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Autosomal recessive disorder recurrence
risk
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Recurrence risk of an autosomal dominant trait
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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
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Mating of two related individuals
Dramatically increases the recurrence risk
of recessive disorders
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Sex-Linked Disorders
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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
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Sex-linked (X-linked) disorders are usually
expressed by males because females have
another X chromosome to mask the
abnormal gene
X-linked recessive
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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
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