Genetics

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Genetics

• U.K. College of Nursing

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Genes and Chromosomes

• Each cell contains 23 pairs of matched
  chromosomes for a total of 46 chromosomes per
  cell.
• One chromosome from each pair is inherited from
  each parent.
• There are 22 pairs of autosomes, which control
  most traits in the body, and one pair of sex
  chromosomes, which determine gender and other
  traits.

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Genes and Chromosomes

• Some genes are dominant and their characteristics
  are expressed even if only on one chromosome.
• Some genes are recessive and their
  characteristics will be expressed only if they
  are carried by both chromosomes in a pair.

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Group Exercise

• Human Variation

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Punnet Squares

• Visual representation of the principles of
  inheritance
• Dominant trait--Capital letter
• Recessive trait--Small letter
• Male vs female trait/gene

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Patterns of Inheritance

• Autosomal Dominant
• Autosomal Recessive
• Sex-Linked (or X-linked) Dominant
• Sex-Linked (or X-linked) Recessive
• Chromosomal Abnormalities
• Congenital Anomalies

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Autosomal Dominant

• Trait appears in every generation (does not skip)
• Both males and females are affected
• Each pregnancy of an affected person has a 50
  chance of producing an affected offspring

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Autosomal Dominant Disorders

• Disorders
• Huntingtons Disease
• Retinitis Pigmentosa
• Polycystic Kidney Disease
• Achodroplasia
• Marfan Syndrome

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Autosomal Dominant Disorders- Marfan Syndrome
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Autosomal Dominant Inheritance
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Autosomal Dominant

• Clinical Situation--
• One parent is unaffected
• One parent carries the defective gene for Marfan
  Syndrome
• Draw the Punnet Square

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Autosomal Dominant Punnett Square
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Autosomal Recessive

• Both parents are usually unaffected, but are
  carriers
• Trait first appears only in siblings rather than
  in parents
• Trait found equally in males and females
• 25 risk when both parents are carriers
• Increased incidence with consanguinity

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Autosomal Recessive

• Disorders
• Phenylketonuria
• Fanconis Anemia
• Tay Sachs Disease
• Sickle Cell Anemia
• Cystic Fibrosis

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Autosomal Recessive Inheritance
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Autosomal Recessive

• Clinical Situation
• Male carries the defective gene for Tay Sachs
  disease
• Female carries the defective gene for Tay Sachs
  disease
• Draw the Punnett Square

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Autosomal Recessive Punnett Square
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X-linked Inheritance

• Sex-Modified Traits - Dominant genes are
  expressed in both males females but at
  differing frequencies
• Ex Baldness - expressed as dominant in males,
  but recessive in females, never as severe in
  females

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X-linked Dominant

• Very rare
• Often lethal in males therefore few males present
  in the pedigree
• Multiple miscarriages may be present
• No carrier status, all individuals with the gene
  are affected
• Trait appears in every generation

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X-linked Dominant

• Female children of affected males will all be
  affected (100 risk) no male to male
  transmission.
• Homozygous females (both X chromosomes are
  affected) have a 100 chance of having an
  affected child of either sex.
• Heterozygous females (only one X affected) have a
  50 of having an affected child with each
  pregnancy.

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X-linked Dominant Disorders

• Hypophosphatemic Rickets
• Fragile X Syndrome

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Fragile X Syndrome
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X-linked Dominant

• Clinical Situation
• Male is affected with hypophosphatemic rickets
• Female is unaffected
• Draw the Punnet square

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X-linked Dominant Punnet Square
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X-linked Recessive

• Incidence of trait much higher among males in a
  kinship than among females
• Trait cannot be transmitted from father to son
• An affected male will pass the carrier status to
  all his daughters
• Female carriers have a 50 risk of transmitting
  the gene to their offspring with each pregnancy

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X-linked Recessive

• Disorders
• Hemophilia A
• Duchennes Muscular Dystrophy
• Color-Blindness

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Duscennes Muscular Dystrophy
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X-Linked Recessive Inheritance
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X-linked Recessive

• Clinical Situation
• Male is affected with Hemophilia A
• Female is normal (non-carrier)
• Draw the Punnett Square
• Use X1 for chomosome with normal allele and X2
  for chromosome with disease allele

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X-linked Recessive Punnet Square
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X-linked Recessive

• Clinical Situation
• Male is normal
• Female is a carrier of color-blindness
• Draw the Punnett Square

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X-linked Recessive Punnett Square
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X-linked Recessive

• Clinical Situation
• Male is affected with Duschenne Muscular
  Dystrophy
• Female is carrier of Duschenne Muscular Dystrophy
• Draw the Punnett Square

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X-linked Recessive Punnett Square
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• Genotype - The actual gene constitution of a
  given person.
• Phenotype - The observable characteristics of a
  given person

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• Traits can be environmentally modified
• type 2 diabetes
• PKU
• Traits can be medically modified
• Sickle cell disease (bone marrow transplant)
• Polycysitc kidney disease (kidney transplant)
• However, genotype stays the same so next
  generation are not saved from condition

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Group Exercise

• Punnet Squares and Patterns of Inheritance

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• Karyotypes
• The arranged representation of the chromosomal
  make-up of a cell nucleus

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Chromosomal Abnormalities

• Abnormalities in number of chromosomes
• Caused by nondisjunction failure of homologous
  chromosomes or sister chromatids to separate
  properly into different progeny cells
• Monosomy - condition in which one chromosome of a
  pair is missing from a somatic cell

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Monosomy X - Turners Syndrome
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Monosomy--Turners Syndrome
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Chromosomal Abnormalities

• Trisomy - condition in which one chromosome in
  the pair is pesent in three copies in a somatic
  cell
• Down Syndrome (21), Trisomy 13 or 18
• Klinefelters Syndrome - XXY

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Abnormalities of Chromosome Number
Trisomy
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Chromosomal Structural Abnormalities

• Deletions - absence of normal chromosomal
  material can be terminal or interstitial
• Duplications - presence of an extra copy of a
  chromosomal segment
• Inversions - Intrachromosomal re-arrangement such
  that the rearranged section is inverted
• Ring Chromosome - Fusion of the ends of a
  chromosome that forms a circle or ring

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Chromosomal Structural Abnormalities

• Translocations - Interchromosomal rearrangement
  can be balanced (all chromosomal material is
  present) or unbalanced (chromosomal material has
  been gained or lost) can be reciprocal or
  Robertsonian

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Structural Abnormalities
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Group Exercise

• Karyotype CD-Rom

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Congenital Anomalies

• Structural abnormalities present at birth
• Are usually not identified with a known genetic
  cause
• Cause may be a combination of genetic and
  environmental factors

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Children at Risk for Congenital Anomalies

• Positive family history of structual anomalies
• Child with one known structural anomaly
• The IUGR infant
• The mentally retarded child
• The unusual appearing child

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Maternal Risk Factors

• Diabetes
• Phenylketonuria (PKU)
• Seizure disorder
• Alcohol and substance abuse
• Recurrent pregnancy loss

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Teratogens

• Environmental substances or exposures that result
  in functional or structural disability.
• Any agent which when given to or ingested by a
  pregnant woman can produce a permanent
  morphologic or functional abnormality.

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Agents Which Cause Teratogenesis

• Drugs and Chemicals Alcohol
• Infections (viruses, TORCH)
• Radiation exposure
• Fat-Soluble Vitamins
• Nicotine
• Heat

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Fetal Susceptibility to Teratogens

• Gestational age at the time of exposure
• Drug dosage
• Route of administration of agent
• Genetic predisposition of fetus to respond to a
  particular agent

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Gestational Susceptibility Factors

• Days 1-17
• Little effect
• Days 18-60
• Period of organogenesis
• Extreme sensitivity to major structural
  abnormalities
• Days 61-270
• Considerably reduced risks
• Functional abnormalities can still occur

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Pedigrees

• A pictorial representation or diagram of the
  family history.
• Allows visualization of relationships of affected
  individuals to other family members.
• May indicate a pattern of inheritance
• Helps pinpoint persons who should be examined or
  tested.

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Pedigree Format

• 3 generations AT LEAST!!
• Note name of informant
• Roman numerals for generations
• Number individuals on pedigree across families

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Pedigree Pointers

• Seek a balance between the need for asking
  specific versus general questions.
• Ask specific questions about each individual as
  you construct the pedigree (birth defects, mental
  retardation, specific traits relevant to the
  diagnosis or concern)
• Ask general questions about the whole family or
  section of a family. Can you think of any family
  characteristics (traits) or medical problems in
  more than one family member?

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Pedigree Reminders

• Multiple reproductive relationships
• Have you had children/pregnancies by anyone
  else?
• Did you have any pregnancies prior to this
  relationship?
• Dont forget half-sibs, abortions, miscarriages,
  stillbirths, previous marriages.

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Pedigree Pointers

• Indicate possible relationships
• Sometimes when there is one family member with
  cleft lip and palate, there are others in the
  family with little indentations in their lower
  lip, heart problems at birth, or poor vision and
  joint pain. Can you think of anyone in your
  family with anything like that?
• Use words the clients will understand
• seizures fits fainting spells

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Group Exercise

• Final Group Work