Transcript Genetic Control of Cell Function and Inheritance

Genetic Control of Cell Function
and Inheritance
NUR 304
Dr. Dory Roedel Ferraro
It’s All in the DNA
• DNA (deoxyribonucleic acid) – extremely
stable macromolecule
• Contains within its structure the basic
information needed to:
– Direct the function of our cells
– Influence our appearance
– Influence how we respond to our environment
– Serve as a unit of inheritance that is passed on
from generation to generation
DNA
• Long, double-stranded helical structure composed of
nucleotides, which consist of phosphoric acid, deoxyribose,
and one of four nitrogenous bases (T,C,A or G)
• Spiral staircase with paired bases representing the steps
• Nitrogenous bases carry the genetic information
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Thymine (T)
Cytosine (C)
Adenine (A)
Guanine (G)
• Precise complimentary pairing of purine and pyrimidine
– A is paired with T
– G is paired with C
Replicating DNA Helix
DNA
• Each nucleotide in a pair is on one strand of the
DNA molecule
• Bases on opposite DNA strands are bound
together by hydrogen bonds
• Double-stranded structure of DNA molecules
allows them to replicate precisely by separation
of the two strands, followed by synthesis of two
new complimentary strands
• Only one strand is used in transcribing
• Both strands are involved in DNA duplication
Chromosomes
• Discrete bundles of DNA containing genetic
information
• Arranged in pairs; one from the mother and one from
the father
• Humans have 23 pairs of chromosomes
• 22 are autosomes (have same appearance in males and
females)
• 23rd pair are the sex chromosomes (determine the sex
of an individual)
– Males have an x and y
– Females have two x chromosomes
Patterns of Inheritance
• Genotype- total sum of the genetic information
that is stored in the genetic code of a person
• Phenotype- represents the recognizable traits,
physical and biochemical, associated with the
genotype
• Expressivity- refers to the expression of a gene in
the phenotype
• Penetrance- the ability of a gene to express its
function
• Gene locus- the point on the DNA molecule that
controls the inheritance of a particular trait
Patterns of Inheritance
• Alleles- alternate forms of a gene (one from each
parent)
• Locus- the position they occupy on the
chromosome
• Alleles at a gene locus may carry recessive or
dominant traits
• Mendelian (single-gene) patterns of inheritance
include autosomal dominant and recessive traits
that are transmitted from parents to their
offspring in a predictable manner
Patterns of Inheritance
• Recessive trait is one expressed only when
two copies (homozygous) of the recessive
alleles are present
• Dominant trait are expressed with either
homozygous or heterozygous pairing of alleles
• Dominant traits are labeled with caps (D)
• Recessive with lower case (d)
Punnett Square
Autosomal Dominant Disorders
• Single mutant gene from an affected parent is
transmitted to an offspring regardless of sex
• The affected parent has a 50% chance of
transmitting the disorder to each offspring
• Unaffected siblings of the offspring do not
transmit the disorder
• In some cases, the person with an autosomal
dominant trait does not have an affected parent,
but rather it is owed to a mutation involving
either the sperm or the ovum
Autosomal Dominant Disorder: Marfan
Syndrome
• Mutation of gene on
chromosome 15
• Prevalence is 1 in 20,000
• Involves CV, skeletal and
ocular systems
• Wide range of variation in
the expression of the
disease
• May have abnormalities
of one or all three
systems
Autosomal Dominant Disorder:
Neurofibromatosis
• Neurogenic tumors that
arise form Schwann
cells
• Type 1 is relatively
common (1 in 3500)
and involves multiple
neural tumors
• Type 2 tumors of the
acoustic nerve
Autosomal Recessive Disorder
• Manifested only when both members of the gene pair
are affected
• Both parents may be unaffected but are carriers of the
defective gene
• Affect both sexes
• Tay-Sachs, Phenylketonuria are autosomal recessive
disorders
• Occurrences
– One in four for affected child
– Two in four for a carrier child
– One in four for a normal child (unaffected, non-carrier)
Chromosomal Disorder: Down
Syndrome
• Most cases are caused by
nondisjunction or an error
in cell division during
meiosis, resulting on a
trisomy of chromosome 21
• Risk of having a child with
Down Syndrome increases
with age
• Condition usually apparent
at birth
• Increased risk of childhood
leukemia
• Increased risk of
Alzheimer’s disease
Maternal Age and Risk of Down
Syndrome
http://www.ndss.org/Down-Syndrome/What-Is-Down-Syndrome/
Turner Syndrome
• An absence of all or part of one
of a female’s X chromosomes
• Affects 1 in 5000 births
• Short stature with normal body
proportions
• Diagnosis often delayed until late
childhood or early adolescence
• Early diagnosis is an important
aspect of treatment allowing for
counseling and screening for
cardiac, renal, thyroid and other
abnormalities
Klinefelter Syndrome
• 47, XXY male
• Testicular dysgenesis
accompanied by the presence of
one or more extra X
chromosomes
• 1 in 500-1000 occurrence
• Congenital hypogonadism
• May have a voice that is highpitched, sparse beard and pubic
hair, female fat distribution
• Infertility is common
Disorders Due to Environmental
Influence
• Physiologic status of the mother
– General state of health (DM associated with
congenital defects)
– Hormone balance
– Nutritional status
– Medications she takes
• Smoking
• Alcohol
• Infectious agents
Teratogenic Agents
• Radiation (microcephaly, skeletal
malformations, intellectual disability)
• Environmental chemicals (mercury)
• Medications and illicit drugs
• Alcohol
• Infectious agents
• Nutrient deficiencies
Medications and Illicit Drugs
• Many drugs can cross the placenta
• Lipid soluble drugs cross more readily and enter
the fetal circulation
• Determining factors
– Rate at which a drug crosses the placenta
– Duration of exposure
– Stage of placental and fetal development at the time
of exposure
– Molecular weight of the drug (< 500 can cross easily)
Sensitivity of Specific Organs
Teratogenic Drugs
• Thalidomide
• Antimetabolites used in the treatment of
cancer
• Anticonvulsants
• Warfarin
• Alcohol
• Cocaine
Alcohol
• Variable effects on fetal development ranging
from minor abnormalities to fetal alcohol
syndrome (FAS)
• Prenatal or postnatal growth retardation
• CNS involvement: neurologic abnormalities,
developmental delays, skull and brain
malformation, characteristic facial features
Clinical Features of Fetal Alcohol
Syndrome
Infectious Agents
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Many microorganisms cross the placenta
TORCH
T=toxoplasmosis (animal excrement)
O=other (varicella zoster, Epstein-Barre,
syphilis)
• R=rubella
• C=cytomegalovirus
• H=herpes simplex type 2
Prenatal Screening and Diagnosis
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Ultrasonography
Maternal serum markers
Non-invasive prenatal testing (NIPT)
Amniocentesis
Chorionic villous sampling
Percutaneous umbilical cord sampling