Mutations
Result from the substitution of one base pair for another, rearrangement of base pairs or by the loss or addition of one or more base pairs
Mutations
________ occur when an error in the process of meiosis or mitosis occur
Mutations
May result from an exposure to harmful substance such as environmental agents, chemicals, and radiation or may be a spontaneous error
Mutations
Somatic ____________ are important causes of cancer and other tumors in which cell differentiation and growth get out of control
Mutations
Most _________ are corrected by the DNA repair mechanisms in the cell
Helpful Mutations
Antibiotic resistance in bacteria
Sickle cell anemia resistance to malaria
Resistance to atherosclerosis
Karyotype
A photograph of a person's chromosomes
Genotype
The genetic composition of a person
Phenotype
The observable expression of a genotype in terms of morphologic, biochemical or molecular traits
Harmful mutations
Humans with mutations resulting in a (theoretically) beneficial trait are generally not viable, because the mutations witch caused the trait, also caused other deformities, and the fetus is miscarried, stillborn, or dies shortly after birth
Mutations in somatic cells
Environmental factors such as ultraviolet radiation from the sun can cause mutations if a mistake is made as DNA copies itself during cell division
Mutations in somatic cells
Acquired (after birth) mutations in somatic cells cannot be passed on to the next generation
Mutations in germ (gametes) cells
If the gene is altered in the germ cell it is not expressed in the individual containing the mutation, but it will be expressed in the next generation
Alleles
Alternate member of gene pairs
Homozygote
Member of a gene pair that is identical
Homozygote
An individual with matching alleles at the same loci on both chromosomes are said to be a ___________
Heterozygote
Member of a gene pair that have different alleles at the same locus
Dominant Alleles
___________ need only be present in one copy to be expressed
Recessive Alleles
_______ Need to be present in two copies to be expressed
Dominant genes
Dominate any situation even if only one parent carries the gene
Recessive genes
Recede in the background, unless both parents carry the gene
Chromosomal disorders
______________ can be a result of alterations in the genetic code sequence, the presence of too many or too few chromosomes on a spot or alterations in the number of chromosomes
Euploid
Normal number of chromosomes
Polyploid
When a Euploid cell has more that the diploid number (23) of chromosomes pairs
Polyploid
A cell containing more than two pairs of chromosomes
Incompatible with life
A zygote having 3 or more copies of each chromosome
Triploidy and metalloids
Account for approximately 10% of all known miscarriages
Metalloids
Cell containing only one copy of the chromosome
Triploidy
69 chromosomes in each somatic cell
Triploidy
Cell containing 3 sets of chromosome
Teraploidy
92 chromosomes in each somatic cell
Teraploidy
Cell containing 4 sets of chromosome
Autosomal aneuploidy
Abnormal number of chromosomes in the cell (usually one more or one less)
Autosomal aneuploidy
A change in the chromosomal number caused by failure of the chromosomes to separate during oogenesis or spermatogenesis
Autosomal aneuploidy
Monosomies and Trisomies are examples of _________________
Monosomies
All are lethal
Monosomies
A cell that is missing a chromosome
Monosomies
If the __________ involves an autosome, the cell will not be viable, however if the cell involves the X chromosome it can be viable and results in a female who has turners syndrome
Trisomies
Some types survive
Trisomies
A cell that contains an extra chromosome
Non-disjunction
Can occur during the 1st or 2nd meiotic division and gives rise to germ cells that have an even # of chromosomes (22 or 23) instead of 23
Trisomy 21
Most common chromosomal disorder is ___________
Trisomy 21
Also known as Down syndrome
Trisomy 21
Extra chromosome in 21 position (3 chromosomes)
Trisomy 21
Incidence of have a child with ____________ increases with age
Trisomy 21
� of all pregnancies end in spontaneous abortions or the fetus being stillborn
Trisomy 21
20% of all children with ___________ die in the first 10 years
Trisomy 21
Children who make it past 10 years of age have a life expectancy of 60 years
Characteristics of Trisomy 21
Non-disjunction is responsible for 95% of cases
Characteristics of Trisomy 21
Caused by a non-disjunction during the first meiotic division, resulting in a trisomy of chromosome 21
Characteristics of Trisomy 21
After a woman is 35 she has a 1/365 chance of having a child with __________________ (reasons unknown)
Characteristics of Trisomy 21
Prenatal diagnosis involves procedures such as amniocentesis (16 weeks gestation) or chronic villus sampling (9-10 weeks gestation) AFP test
AFP Test
Low results indicate possible Down syndrome (trisomy 21)
What are some of the Clinical features of Trisomy 21
Patients have distinct facial features (lg. forehead, broad nasal bridge, wide spaced eyes, lg. protruding tongue, sm. Low set ears)
What are some of the Clinical features of Trisomy 21
Patients have developmental delays (some degree of mental retardation)
What are some of the Clinical features of Trisomy 21
1/3 of the patients suffer from a congenital heart defect
What are some of the Clinical features of Trisomy 21
Patients have an increased risk of leukemia
What are some of the Clinical features of Trisomy 21
Patients are at risk for premature aging
What are some of the Clinical features of Trisomy 21
Patients have an increased risk of developing Alzheimer's
Sex chromosome Aneuploidy
1:400 males and 1:650 females have a form of ___________________
Sex chromosome Aneuploidy
Klinefelters syndrome, turner syndrome, XXX syndrome, XYY syndrome,
Sex chromosome Aneuploidy
_______________ can be caused by deletion, duplication, inversions, translocations, and fragile sites
Klinefelter syndrome
47, XXY karyotype
Klinefelter syndrome
Male patients are born with an extra X chromosome
Klinefelter syndrome
In rare cases of __________ there may be more than one extra X (XXXXY)
Klinefelter syndrome
One of the most common genetic abnormalities
Klinefelter syndrome
Male patients are sterile, and have enlarged breasts, sparse facial and body hair, sm. Testies/penis, and tall abnormally proportioned bodies
Turner Syndrome
45 X Karyotype
Turner Syndrome
Female patients are born with the absence of all or part of an X chromosome
Turner Syndrome
Female patients are sterile, have no ovaries, webbing of neck, their breasts do not develop well and they have widely spaced nipples, they are short with a stocky build, and they have coarctation of their aorta (narrowing)
Deletion
Absent section of DNA
Deletion
When a chromosome is absent; either entirely or by only a portion
Deletion
A ______________ deletion of chromosome 5 causes cru de chat syndrome "cry of the cat
Duplication
Repeated gene or gene sequence
Duplication
More compatible with life than deletion
Duplication
A _____________of the chromosome 5 causes mental retardation but physical characteristics are nearly normal
Inversions
When the chromosome is broken at 2 points and is followed by reinsertion of missing fragment at its original site but in inverted order. Instead of ABCDE it is ACBDE
Inversions
When the chromosome has an ______________ genetic information is not lost or gained
Inversions
When the chromosome has an_______________it may or may not result in an abnormality
Inversions
Serious problems usually occur in the offspring of the person with the _______________
Translocation
Occurs when two different (none homologous) chromosomes break and rejoin in an abnormal arrangement
Translocation
There are two types, balanced (reciprocal) __________ and Robersonian _____________
Translocation
Usually shows up in the offspring of the individuals who have the _________________
Translocation
Usually shows up in the offspring of the individuals who have the _________________
Translocation
Example of _____________ is leukemia, breast cancer, schizophrenia, muscular dystrophy and Downs's syndrome, 5% of recurrent miscarriage
Balanced (reciprocal) translocation
No genetic info is lost, may have normal or abnormal babies
Robertsonian translocation
Break occurs near the centromere, affecting the short arm of one chromosome and the long arm of the other.
Fragile sites
Areas on the chromosome break or have gaps for unknown reasons
Fragile sites
Most of the _________________ have no apparent relationship to disease except one _____________ on the lone arm of X which leads to Fragile X syndrome (the gene is called FMR1)
Fragile site syndrome
Most important feature is mental retardation
Fragile site syndrome
Has a high population prevalence 1:2000 boys and 1:4000 girls are estimated to be affected
Fragile site syndrome
Approximately 1/400 individuals in the general population are believed to carry the gene
Fragile site syndrome
There is a pattern of inheritance, carrier men pass the permutation to their daughters, but none of their sons, and each child from a carrier woman has a 50% chance of inheriting the gene
Single-Gene disorders
Include Autosomal dominant, Autosomal Recessive, X-linked recessive, and X-linked dominant inheritance
Autosomal dominant
Male and females are equally affected
Autosomal dominant
One of the parents is AFFECTED, there are NO silent Carriers, and unaffected people do NOT transmit the disease
Autosomal dominant
Defect present in only one of the alleles produces the clinical expression of the disease
Autosomal dominant
If one parent has the disease there is a 50% probability that the children will have the disease
Autosomal dominant
If both parents have the disease all their children will have the disease
Autosomal dominant
Examples of ________________ diseases include Marfans Syndrome, Huntington's chorea, Familial Hypercholesterolemia, and Achrondroplasia
Penetrance
______________is a measure of the proportion of individuals in a population who carry a specific gene and express the related trait
Reduced penetrance
An individual has the genotype for the disease, but may or may not express the disease phenotype
Retinoblastoma
A person with ____________may inherit an altered copy of the gene from one parent, or the altered gene may be the result of a new mutation
Variable expression
Complete gene penetrance; however severity of disease is variable within the same family.
Delayed age of onset
Genotype for disease id present at birth, however the disease does not express itself until adulthood
Delayed age of onset
An example of ___________________ is Huntington's disease. The typical age f onset is between ages 30 and 45 but there is a juvenile type.
Huntington's disease
When a patient has _____________ they have usually inherited the altered gene from one affected parent.
Huntington's disease
Progressive brain disorder that causes uncontrolled movements, mental and emotional problems, and the loss of cognition
Plitrophy
One gene mutation causes effects on multiple body systems or structures
Plitrophy
A good example of _________________ is Marfans disease
Marfans disease
A disorder of connective tissue which causes skeletal defects
Marfans disease
Patient is tall and lanky, with long limbs and spider like fingers, chest abnormalities, has curvature of the spine, crowded teeth and heart abnormalities
Autosomal recessive inheritance
Male and female are equally affected
Autosomal recessive inheritance
Parents may just be carriers, and both parents must pass on a recessive gene to produce an affected (homozygous) child
Autosomal recessive inheritance
If both parents are affected, all their offspring will be affected
Autosomal recessive inheritance
If the child has one normal gene and one defective gene (heterozygous), that child becomes a carrier and shows no clinical sign of the disease
Autosomal recessive inheritance
With two carrier parents a child has a 25% of becoming affected, 50% chance of becoming a carrier and a 25% chance of being normal
Autosomal recessive inheritance
With one carrier parent and one normal parent a child has a 50% chance of being a carrier
Autosomal recessive inheritance
With one affected parent and one normal parent a child has a 100% chance of being a carrier
Autosomal recessive inheritance
Examples of ___________________ are Cystic fibrosis, Tay-Sach, Phenylketonuria, and sickle-cell trait.
Tay-Sach
Patient seems normal at birth, however manifests progressive weakness, muscle flaccidity, and rapid deterioration of motor and mental function, etc....
Tay-Sach
Death usually happens by age 4
Phenylketonuria
Deficiency of liver enzymes that converts the amino acid phenylalanine to tyrosine, so toxic levels of phenylalanine accumulate in the blood/tissue.
Phenylketonuria
(PKU)
Phenylketonuria
Can cause signs of mental retardation, delayed speech, and other signs of impaired neuro development
Consanguinity
Mating's of related individuals
Consanguinity
Can increase risk of autosomal recessive disease
boys
XY
girls
XX
X-linked recessive inheritance
Usually carried by the female sex chromosome
X-linked recessive inheritance
Since males only receive one X chromosome, they will be affected by the disease; men are always more affected by sex-linked diseases than woman
X-linked recessive inheritance
Carrier females have a 50% chance of producing an affected make child and an equal chance of producing carrier female child with each pregnancy
X-linked recessive inheritance
Affected males will transmit the defect to all their daughters, (who then become carriers) and none of their sons
X-linked recessive inheritance
Examples of ________________ are Duchenne's muscular dystrophy, Hemophilia A, Fragile X syndrome, Aneuploidy, Trisomy, and Polyploid
Fragile X syndrome
Males are affected more than females
Fragile X syndrome
Patients are mentally retarted, have long faces, lg. mandibles, lg. everted ears, and lg. testicles.
X-linked Dominant disorder
Only a few known diseases exist and they are seldom encountered
X-linked Dominant disorder
If father has a ___________, all of his daughters and none of his sons will be affected.
X-linked Dominant disorder
If mother has a _____________there is a 50% chance each of her children will be affected
X-linked Dominant disorder
Examples of _____________Deafness, incontinentia Pigmeni, Familial rickets and hereditary nephritis.
Multifactorial Inheritance
Is similar to polygenic traits but also includes environmental effects on genes
Multifactorial Inheritance
Is caused from multiple genes
Multifactorial Inheritance
_______________that are expressed later in life include Primary hypertension, diabetes mellitus, some cancers, and schizophrenia
Multifactorial Inheritance
_______________that are expressed at birth (congenital) include cleft lip/palate, club foot, and congenital heart disease
Familial patterns of inheritance
Disease with _____________________include Coronary artery disease, hypertension, breast cancer, colorectal cancer, diabetes (type 1 and 2), alcoholism, Alzheimer's disease, schizophrenia, and bipolar affective disorder
Genetic counseling
Patient that should have ____________ include patients with known genetic diseases in the family and Patients that are adoptees without information on genetic heritage
Genetic counseling
Process of evaluation includes a pedigree analysis and gene mapping
Genetic counseling
Diseases requiring _________________ include autosomal dominant and recessive disorders, sickle cell anemia, x-linked disorders, hemophilia A, known genetic or chromosomal abnormalities, maternal pattern deafness
Pedigree analysis
A graphic method of portraying a family history of an inherited trait
Pedigree analysis
Constructed from a carefully obtained family history
Pedigree analysis
Is useful for tracing the pattern of inheritance for a particular trait
Pedigree analysis
Reliable predictions of whether a member of a family will develop the disease can be made through a _____________________
Gene mapping
______________ can find the location of genes on chromosomes
Gene mapping
The location of a gene can tell much about the function of the gene, its interaction with other genes, and the likelihood that certain individuals will develop a genetic disease
Gene mapping
Example of ___________ is the human genome project
Teratogens
A __________is an agent or substance that may cause physical defects in the developing embryo or fetus when a pregnant female is exposed to that substance
Teratogens
If the period of exposure to a _________ is from fertilization through early implantation (post fertilization days 0-15), the effect of an insult is often all or nothing; implantation failure or spontaneous abortion would be the likely outcome
Teratogens
If the period of exposure to a _________ is from the second stage of development, the period of organogenesis (day 15-60), anatomical malformations may be induced
Teratogens
If the period of exposure to a _________ is from the third stage, the period of fetal development during the second and third trimesters of pregnancy, exposures may lead to growth restriction, stillbirth, or impaired cognitive development
Teratogens
Agents of _____________ include radiation, drugs, alcohol, chemical substances, and infectious agents such as viruses
Teratogens
Environmental ___________include radiation, viruses, and chemicals
Genes may predispose
while the enviornment triggers genetic defects
Gene technology
Current use and future potential for DNA manipulation, DNA cloning, Biochip
Biochip
Squares of glass etched with DNA strands and can be used for genetic screening, research and diagnosis
Genetic research
______________ includes development of drugs and vaccines, agricultural applications, pesticide and pest resistant crops and hybrid animals, stem cell research.