D115 Pathophysiology Study Guide
Unit 2: Foundations of Pathophysiology: Genes, Lifestyle, and Immunity
Genetic Influence on Patient Outcomes-page 13-15
Vocabulary:
RNA
• Ribonucleic acid (RNA)-single strand
• Messenger carrying instructions from DNA for making proteins (messenger for making proteins)
• Messenger RNA = mRNA
• Nitrogenous bases
o Adenine –Uracil
o Guanine -- Cystosine
DNA
• Deoxyribonucleic acid (DNA)-double strand
• Primary constituent of chromosomes
• Molecule composed of two polynucleotide chains that coil around each other to form a double helix carrying genetic instructions for the
development, functioning, growth and reproduction of all known organisms and many viruses.
• Molecule that contains the biological instructions that make each species unique
• DNA along with the instructions it contains, is passed from adult organisms to their offspring during reproduction
• Nitrogenous bases-
o Adenine – Thymine
o Guanine -- Cytosine
!
Chromosomes
• Threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes
!
,Mitosis
• Mitosis is a process of cell duplication, in which one cell divides into two genetically identical daughter cells. In the various stages of
mitosis, the cell’s chromosomes are copied and then distributed equally between the two new nuclei of the daughter cells.
Transcription
• Transcription is the first step in gene expression. It involves copying a gene's DNA sequence to make an RNA molecule.
• Transcription is performed by enzymes called RNA polymerases, which link nucleotides to form an RNA strand (using a DNA strand as a template).
• Transcription has three stages: initiation, elongation, and termination.
• In eukaryotes, RNA molecules must be processed after transcription: they are spliced and have a 5' cap and poly-A tail put on their ends.
• Transcription is controlled separately for each gene in your genome.
Translation
• Transcription factors bind to DNA sequences called transcription factor-binging sites near genes to regulate the timing of transcription, as
well as the specific tissues in which genes are actively transcribed
Phenotype
• Reflects the interaction of genotype and environment
• A phenotype is an individual’s observable traits, such as height, eye color, and blood type. The genetic contribution to the phenotype is
called the genotype. Some traits ae largely determined by the genotype, while other traits are largely determined by environmental
factors.
Genotype
• A person’s genetic makeup
• A genotype is an organism’s complete set of genetic material. Often though, genotype is used to refer to a single gene or set of genes, such
as the genotype for eye color. The genes take part in determining the characteristics that are observable (phenotype) in an organism, such as
hair color, height, etc.
• The composition of genes at a given locus (specific physical location of a gene or DNA sequence) is known as the genotype. The outward appearance
of an individual, which is the result of both genotype and environment, is the phenotype (see also Chapter 6, Epigenetics). For example, an infant
who is born with an inability to metabolize the amino acid phenylalanine has the single-gene disorder known as phenylketonuria (PKU) and thus has
the PKU genotype. If the condition is left untreated, abnormal metabolites of phenylalanine will begin to accumulate in the infant's brain and
irreversible intellectual disability will occur. Intellectual disability is thus one aspect of the PKU phenotype. By imposing dietary restrictions to limit
the intake of food containing phenylalanine, however, cognitive impairment can be prevented. Although the child still has the PKU genotype, a
modification of the environment (in this case the child's diet) produces an outwardly normal phenotype.
Dominant/recessive
• In many loci the effects of one allele mask those of another when the two are found together in a heterozygote. The allele whose effects are
observable is said to be dominant. The allele whose effects are hidden is said to be recessive (from the Latin root for “hiding”). Traditionally, for loci
having two alleles, the dominant allele is denoted by an uppercase letter and the recessive allele is denoted by a lowercase letter. When one allele is
dominant over another, the heterozygote genotype Aa has the same phenotype as the dominant homozygote AA. For the recessive allele to be
expressed, it must exist in the homozygote form, aa.
Autosomal dominance
• Autosomal means it is only found within the non-sex chromosomes.
• Dominant means that a single copy of the disease-associated mutation is enough to cause the disease
• Skipped generations are not seen in classic autosomal dominant pedigrees
Autosomal recessive
• Autosomal means it is only found within the non-sex chromosomes
• Recessive means that two copies of an abnormal gene must be present in order for the disease or trait to develop.
X linked
• A trait where a gene is located on the X chromosome. Humans have two sex chromosomes, X and Y. In an X-linked or sex-linked disease, it
is usually males that are affected because they have a single copy of the X chromosome that carries the mutation
, !
!
Evaluation of pedigrees
• Pedigree charts are an important tool in the analysis of modes of inheritance
• With complications such as incomplete or age-dependent penetrance, variable expressivity, and sex-influenced traits, it is not always possible simply
to look at a disease pedigree and determine the mode of inheritance. Sophisticated statistical approaches have evolved to deal with such
complications. Incorporated into computer programs, these statistical techniques assess the probability of observing a certain pedigree if a
particular mode of inheritance (e.g., autosomal dominant with incomplete penetrance) is in effect.
Incident rate
• The number of new cases of a disease reported during a specific period (typically 1 year) divided by the number of individuals in the
population. The denominator is often expressed as person-years.
• Prevalence includes all cases (new and pre-existing cases) in the population at the specified time
Prevalence rate
• The proportion of the population affected by a disease at a specific point in time. Prevalence is thus determined by both the incidence
rate and the length of survival period in affected individuals
• Limited to new cases only
Relative risk
• The ratio of the incidence rate among individuals with a given risk factor to the incidence rate among those without it:
!
Key Questions
1. What are genes composed of and where are they located?
• Genes, the basic units of inheritance, are composed of DNA and are located on the chromosomes
• Serve as the blueprints of proteins in the body, influencing all aspects of body structure and function
• Humans have approximately 20,000 to 25,000 genes
• An error in one of these genes can lead to a recognizable genetic disease
2. What are the four types of nitrogenous bases that constitute DNA?
o Adenine – Thymine
o Guanine -- Cytosine
3. How are new strands of DNA formed?
• Through replication.
• DNA replication consists of the breaking of the weak hydrogen bonds between the bases, leaving a single strand with each base unpaired. The
consistent pairing of adenine with thymine and of guanine with cytosine, known as complementary base pairing, is the key to accurate
replication. The principle of complementary base pairing dictates that the unpaired base will attract a free nucleotide only if the nucleotide has
the proper complementary base. Thus a portion of a single strand with a sequence of bases labeled ATTGCT will bond with a series of free
nucleotides with the bases TAACGA. When replication is complete, a new double-stranded molecule identical to the original is formed (Fig.
4.3, A). The single strand is said to be a template (guide), or molecule on which a complementary molecule is built, and is the basis for
synthesizing the new double strand.
, 4. How is the process of transcription regulated?
• Through proteins called transcription factors
• Transcription factors can either activate or repress the expression of genes
5. How many pairs of chromosomes do humans have?
• 46 total, or 23 pairs (one set from mother (XX), one set from father (XY))
6. What are some of the most common types of chromosome abnormalities?
• Chromosome aberrations and associated diseases
o Leading known cause of intellectual disability and spontaneous pregnancy loss
o Polyploidy- a condition in which a euploid cell has some multiple of the normal number of chromosomes. Humans have been
observed to have triploidy (three copies of each chromosome) and tetraploidy (four copies of each chromosome): both
conditions are lethal.
o Aneuploidy- cells that do not contain a multiple of 23 chromosomes
▪ Trisomy-cell containing three copies of one chromosome
• Down syndrome- trisomy of the 21 chromosome
• IQ 25-70
• Congenital heart defects
• Reduced ability to fight respiratory tract infections
• Increased susceptibility to leukemia
• By age 40 the virtually always develop symptoms of Alzheimer’s disease because one of the genes that
can cause Alzheimer’s is located on chromosome 21
• ¾ of fetuses known to have Down Syndrome are spontaneously aborted or still born
• Avg life expectancy is 60 years
• More likely to occur in the offspring of women over 35 years old
• Sex Chromosome Aneuploidy
• 47,XXX karyotype
o Female (no Y0
o Tall
o Learning problems
• 45,X karyotype (Turner syndrome)
o Most common single-chromosome aberration is the 45, X
o Always female because they have no Y chromosome
o Usually sterile, however, and have gonadal streaks rather than ovaries
o Short stature
o Webbing of the neck in about half the cases
o Widely spaced nipples
o Coarctation (narrowing) of the aorta
o Edema of the feet in newborns
o Sparse body hair
o IQs typically normal but some impairment of spatial and mathematical
reasoning ability
! o ¾ inherit their X chromosome from the mother
(Turner Syndrome) • 47,XXY karyotype (Klinefelter syndrome)
o Have at least two X chromosomes and a Y chromosome in each cell
o Have a male appearance because of the presence of a Y chromosome
o Usually sterile and about half develop female-like breasts (gynecomastia)
o High pitched voice
o Testes are small and body hair sparse
o Moderate degree of mental impairment
• 47, XYY karyotype
o Taller than average
o 10-15 point reduction in IQ
o Significantly elevated in prison populations
▪ Might predispose affected individuals to violent, criminal behavior
!
(Klinefelter Syndrome)
Unit 2: Foundations of Pathophysiology: Genes, Lifestyle, and Immunity
Genetic Influence on Patient Outcomes-page 13-15
Vocabulary:
RNA
• Ribonucleic acid (RNA)-single strand
• Messenger carrying instructions from DNA for making proteins (messenger for making proteins)
• Messenger RNA = mRNA
• Nitrogenous bases
o Adenine –Uracil
o Guanine -- Cystosine
DNA
• Deoxyribonucleic acid (DNA)-double strand
• Primary constituent of chromosomes
• Molecule composed of two polynucleotide chains that coil around each other to form a double helix carrying genetic instructions for the
development, functioning, growth and reproduction of all known organisms and many viruses.
• Molecule that contains the biological instructions that make each species unique
• DNA along with the instructions it contains, is passed from adult organisms to their offspring during reproduction
• Nitrogenous bases-
o Adenine – Thymine
o Guanine -- Cytosine
!
Chromosomes
• Threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes
!
,Mitosis
• Mitosis is a process of cell duplication, in which one cell divides into two genetically identical daughter cells. In the various stages of
mitosis, the cell’s chromosomes are copied and then distributed equally between the two new nuclei of the daughter cells.
Transcription
• Transcription is the first step in gene expression. It involves copying a gene's DNA sequence to make an RNA molecule.
• Transcription is performed by enzymes called RNA polymerases, which link nucleotides to form an RNA strand (using a DNA strand as a template).
• Transcription has three stages: initiation, elongation, and termination.
• In eukaryotes, RNA molecules must be processed after transcription: they are spliced and have a 5' cap and poly-A tail put on their ends.
• Transcription is controlled separately for each gene in your genome.
Translation
• Transcription factors bind to DNA sequences called transcription factor-binging sites near genes to regulate the timing of transcription, as
well as the specific tissues in which genes are actively transcribed
Phenotype
• Reflects the interaction of genotype and environment
• A phenotype is an individual’s observable traits, such as height, eye color, and blood type. The genetic contribution to the phenotype is
called the genotype. Some traits ae largely determined by the genotype, while other traits are largely determined by environmental
factors.
Genotype
• A person’s genetic makeup
• A genotype is an organism’s complete set of genetic material. Often though, genotype is used to refer to a single gene or set of genes, such
as the genotype for eye color. The genes take part in determining the characteristics that are observable (phenotype) in an organism, such as
hair color, height, etc.
• The composition of genes at a given locus (specific physical location of a gene or DNA sequence) is known as the genotype. The outward appearance
of an individual, which is the result of both genotype and environment, is the phenotype (see also Chapter 6, Epigenetics). For example, an infant
who is born with an inability to metabolize the amino acid phenylalanine has the single-gene disorder known as phenylketonuria (PKU) and thus has
the PKU genotype. If the condition is left untreated, abnormal metabolites of phenylalanine will begin to accumulate in the infant's brain and
irreversible intellectual disability will occur. Intellectual disability is thus one aspect of the PKU phenotype. By imposing dietary restrictions to limit
the intake of food containing phenylalanine, however, cognitive impairment can be prevented. Although the child still has the PKU genotype, a
modification of the environment (in this case the child's diet) produces an outwardly normal phenotype.
Dominant/recessive
• In many loci the effects of one allele mask those of another when the two are found together in a heterozygote. The allele whose effects are
observable is said to be dominant. The allele whose effects are hidden is said to be recessive (from the Latin root for “hiding”). Traditionally, for loci
having two alleles, the dominant allele is denoted by an uppercase letter and the recessive allele is denoted by a lowercase letter. When one allele is
dominant over another, the heterozygote genotype Aa has the same phenotype as the dominant homozygote AA. For the recessive allele to be
expressed, it must exist in the homozygote form, aa.
Autosomal dominance
• Autosomal means it is only found within the non-sex chromosomes.
• Dominant means that a single copy of the disease-associated mutation is enough to cause the disease
• Skipped generations are not seen in classic autosomal dominant pedigrees
Autosomal recessive
• Autosomal means it is only found within the non-sex chromosomes
• Recessive means that two copies of an abnormal gene must be present in order for the disease or trait to develop.
X linked
• A trait where a gene is located on the X chromosome. Humans have two sex chromosomes, X and Y. In an X-linked or sex-linked disease, it
is usually males that are affected because they have a single copy of the X chromosome that carries the mutation
, !
!
Evaluation of pedigrees
• Pedigree charts are an important tool in the analysis of modes of inheritance
• With complications such as incomplete or age-dependent penetrance, variable expressivity, and sex-influenced traits, it is not always possible simply
to look at a disease pedigree and determine the mode of inheritance. Sophisticated statistical approaches have evolved to deal with such
complications. Incorporated into computer programs, these statistical techniques assess the probability of observing a certain pedigree if a
particular mode of inheritance (e.g., autosomal dominant with incomplete penetrance) is in effect.
Incident rate
• The number of new cases of a disease reported during a specific period (typically 1 year) divided by the number of individuals in the
population. The denominator is often expressed as person-years.
• Prevalence includes all cases (new and pre-existing cases) in the population at the specified time
Prevalence rate
• The proportion of the population affected by a disease at a specific point in time. Prevalence is thus determined by both the incidence
rate and the length of survival period in affected individuals
• Limited to new cases only
Relative risk
• The ratio of the incidence rate among individuals with a given risk factor to the incidence rate among those without it:
!
Key Questions
1. What are genes composed of and where are they located?
• Genes, the basic units of inheritance, are composed of DNA and are located on the chromosomes
• Serve as the blueprints of proteins in the body, influencing all aspects of body structure and function
• Humans have approximately 20,000 to 25,000 genes
• An error in one of these genes can lead to a recognizable genetic disease
2. What are the four types of nitrogenous bases that constitute DNA?
o Adenine – Thymine
o Guanine -- Cytosine
3. How are new strands of DNA formed?
• Through replication.
• DNA replication consists of the breaking of the weak hydrogen bonds between the bases, leaving a single strand with each base unpaired. The
consistent pairing of adenine with thymine and of guanine with cytosine, known as complementary base pairing, is the key to accurate
replication. The principle of complementary base pairing dictates that the unpaired base will attract a free nucleotide only if the nucleotide has
the proper complementary base. Thus a portion of a single strand with a sequence of bases labeled ATTGCT will bond with a series of free
nucleotides with the bases TAACGA. When replication is complete, a new double-stranded molecule identical to the original is formed (Fig.
4.3, A). The single strand is said to be a template (guide), or molecule on which a complementary molecule is built, and is the basis for
synthesizing the new double strand.
, 4. How is the process of transcription regulated?
• Through proteins called transcription factors
• Transcription factors can either activate or repress the expression of genes
5. How many pairs of chromosomes do humans have?
• 46 total, or 23 pairs (one set from mother (XX), one set from father (XY))
6. What are some of the most common types of chromosome abnormalities?
• Chromosome aberrations and associated diseases
o Leading known cause of intellectual disability and spontaneous pregnancy loss
o Polyploidy- a condition in which a euploid cell has some multiple of the normal number of chromosomes. Humans have been
observed to have triploidy (three copies of each chromosome) and tetraploidy (four copies of each chromosome): both
conditions are lethal.
o Aneuploidy- cells that do not contain a multiple of 23 chromosomes
▪ Trisomy-cell containing three copies of one chromosome
• Down syndrome- trisomy of the 21 chromosome
• IQ 25-70
• Congenital heart defects
• Reduced ability to fight respiratory tract infections
• Increased susceptibility to leukemia
• By age 40 the virtually always develop symptoms of Alzheimer’s disease because one of the genes that
can cause Alzheimer’s is located on chromosome 21
• ¾ of fetuses known to have Down Syndrome are spontaneously aborted or still born
• Avg life expectancy is 60 years
• More likely to occur in the offspring of women over 35 years old
• Sex Chromosome Aneuploidy
• 47,XXX karyotype
o Female (no Y0
o Tall
o Learning problems
• 45,X karyotype (Turner syndrome)
o Most common single-chromosome aberration is the 45, X
o Always female because they have no Y chromosome
o Usually sterile, however, and have gonadal streaks rather than ovaries
o Short stature
o Webbing of the neck in about half the cases
o Widely spaced nipples
o Coarctation (narrowing) of the aorta
o Edema of the feet in newborns
o Sparse body hair
o IQs typically normal but some impairment of spatial and mathematical
reasoning ability
! o ¾ inherit their X chromosome from the mother
(Turner Syndrome) • 47,XXY karyotype (Klinefelter syndrome)
o Have at least two X chromosomes and a Y chromosome in each cell
o Have a male appearance because of the presence of a Y chromosome
o Usually sterile and about half develop female-like breasts (gynecomastia)
o High pitched voice
o Testes are small and body hair sparse
o Moderate degree of mental impairment
• 47, XYY karyotype
o Taller than average
o 10-15 point reduction in IQ
o Significantly elevated in prison populations
▪ Might predispose affected individuals to violent, criminal behavior
!
(Klinefelter Syndrome)
