Genes
1. DNA sequences that that code for one or more specific proteins (in the nucleus)
2. Partially compose chromosomes
3. Everyone inherits one complete (and slightly varying) set from each parent - inherit one of each pair of autosomes and one sex chromosom
Genetics
The study of genes and their transmission through generation
Genome
Sum total of an organism's DNA (may not all code for proteins though)
Note- in genotype to phenotype slide, the genome is on the bottom with each box representing a gene (exons) that codes for certain proteins
Gene (singular)
A segment of DNA- there are about 22,000 different genes on 23 pairs of chromosomes
Human Chromosomes
1. Partially composed of DNA
2. 23 pairs in all
a. 22 pairs of autosomes
b. one pair of sex chromosomes
Genotype
1. A person's complete set of alleles
2. Helps define your phenotype
3. Inherited
Phenotype
1. Observable physical and functional traits / the physical or functional expression of the alleles that make up our genotype
2. Visible and not (hair color as well as blood type and disease susceptability)
3. Determined by genotype, environmental factors
Mutations
Random changes to the DNA sequence
Human gene pool
1. all the various genes and their alleles in the human population (account for differences among people)
2. There are so many alleles in our 22,000 genes means individuals are all different
Autosomes
1. Humans have 22 pairs of them
2. Type of chromosomes
3. Each autosome carries the same genes at the locus
- nucleotides can vary though = alleles
homologous chromosomes
1. Chromosomes that look like and have a copy of each gene at the same location on the chromosome
2. Both autosomes and pair of X-chromosomes in females can be considered this
Locus
The location of a specific pair of genes on the chromosome
Alleles
1. Alternative versions of the same gene (usually a pair of genes has the same structure and function)
2. Produced from sequence differences in genes (different nucleotide sequence)
3. Can lead to different proteins (that cause different functions)
4. A s
Homozygous for some gene
Means that you possess 2 identical alleles of a particular gene
ex. AA
If you possess two different alleles (version) of a gene:
you are heterozygous for that gene
ex. Aa
Cause of different alleles?
Uncorrected mutations in cells that became sperm or eggs that were passed on
Punnet square
1. A simple way to represent patterns of inheritance of alleles
2. Shows possible genotypes of offspring
3. Each axis has one parents 2 copies of their chromosomes from which they donate 1 to their offspring
Gregor Mendel
1. 1865 Austrian monk
2. Used green and yellow pea plants as model organisms to figure out dominant/recessive
3. Laws: Segregation and Independent Assortment
One-trait cross
Mendel followed the inheritance of a single trait (like color or texture)
Law of Segregation
1. Mendel's first rule of inheritance
2. When gametes are formed in parents:
1. The two alleles of each gene ("factor of heredity") separate from each other so each gamete recieves only one allele of each gene (and gets one from each parent)
2. the allele
Gametes
1. Haploid
2. Half the number of chromosomes and genes as the parent
Recessive
1. An allele that behaves in a recessive manner is only visible when the allele behaving in the dominant manner is not present
2. Usually depicted as a lower case letter
Homozygous recessive
Visible recessive phenotype (like straight hairline or CF)
Most recessive alleles are harmless of the homozygous recessive person- so why are they in human gene pool?
They originated as mutations at some point in time and remain there because they are harmless
Harmful recessive alleles:
1. Mutated nucleotide sequence causes them to not code for a needed protein
2 Can cause certain problems- like cystic fibrosis
3. Even if homozygous recessives all dies (prematurely from the gene) the allele would persist in the gene pool through heterozy
Dominant alleles refers to...
1. How an allele behaves with regard to a recessive allele in a heterozygote
2. Not necessarily more common
3. Controls the phenotype in a heterozygote
example- polydactyly is the rare possession of a dominant allele that causes extra fingers and toes
Cystic Fibrosis- Who has it?
1. Most common fatal genetic disease in N. America
2. About 30,000 people have it in US (not really a useful number)
2. 1 in 23 Caucasians (and 1 in 31 Americans) carry recessive defective allele (no symptoms)
3. 1 in 2,000 US Whites gets it; 1 in 17,000
Cystic Fibrosis (progressive pulmonary disease) - caused by:
1. Mutation in a single gene (CFTR)
2. It produces a defective version of CFTR protein
a. This protein normally helps in chloride transport across cell membrane of epithelial cells
b. The impairment of this process means cells do not release chloride (blo
The effects of the thick sticky mucus produced by several organs in people with cystic fibrosis:
1. Clogged Lungs = inflammation and infections that can be fatal
2. Blocked Pancreas - blocks ducts and prevents digestive enzymes from reaching intestines (and digesting food)
3. Sweat glands - affected but not really a problem
Cystic Fibrosis Treatment
There is no cure, but there are improvements in symptomatic treatments
1. Chest thumping to dislodge mucus
2. Antibiotics to treat lung infections
(have increased life expectancy from 5 to 37)
Symptoms of Cystic Fibrosis
1. Coughing, wheezing
2. Pneumonia
3. Big appetite but no weight gain
4. Foul smelling bulky feces
5. Salty skin
Cystic Fibrosis Diagnosis
1. Usually diagnosed by age 3
2. Test for high salt levels in perspiration
- in old days they used to lick the head of babies
3. DNA-based blood test can screen for variation in gene responsible
Gene Therapy as a possible treatment for cystic fibrosis: The Process
1. Began in 1990
2. Focuses on correcting the faulty CFTR genes
a. 1993- inserted a copy of normal gene into a common cold virus ("vector")
2. Virus carried normal genes to CFTR cells through airways of the lungs
3. Have now also tried other methods of ge
A mating between 2 parents that are heterozygous (Ww) for a trait:
Can produce offspring that are heterozygous or homozygous:
WW; Ww; Ww; ww
Predicting the results of a 2 trait cross:
1. Each parent donates one allele of each gene to gamete
2. These genes for different traits assort independently of each other
Mendel's Law of Independent Assortment
Mendel's Law of Independent Assortment
Alleles of different genes are distributed to egg and sperm cells independently of each other during formation of the sperm or egg
Though we now know that this only applies to genes located on different chromosomes!
Incomplete Dominance
The heterozygous genotype results in a phenotype that is intermediate between the two homozygous phenotypes
(Mendel's laws state that only one allele will be expressed)
examples
1. wavy hair results because neither straight or curly is dominant
2. familia
Codominance
Products of both alleles are expressed equally
examples =
1. AB blood type
2. sickle cell anemia
Dominance in the gene for blood type:
1. Three alleles for the blood type gene
2. O is recessive
3. A and B are codominant = if heterozygous with an A and B allele you have type AB blood with both A and B antigens on your red blood cells
Genotype of people with Sickle Cell Anemia
Hb^sHb^s
You must be homozygous for for sickle cell anemia- have only the bad hemoglobin (Hb^s hemoglobin) in your red blood cells
Possible genotypes for a person with Type B blood:
BB
BO
Displays B surface antigens
Sickle cell anemia- How it is inherited
1. One of 2 alleles codes for a hemoglobin molecule (Hb^s) that is different from normal hemoglobin molecule (Hb^A) by one amino acid
2. Mating between two people with sickle cell anemia trait can result in offspring that are:
1. Homozygous for sickle cel
What happens when you have sickle cell anemia to make you sick?
1. Air with lower oxygen levels causes Hb^s hemoglobin to crystallize in red blood cells 2. They sickle
3. These cells:
a. rupture easily
b.Clog blood vessels and block blood flow
c. Carry less oxygen to tissue and organs
Symptoms of Sickle Cell Anemia
Oxygen deprivation causes:
fatigue, chest pain, bone and joint pain, jaundice, retinal damage
Untreated it causes:
stroke, blindness, pneumonia, and other health problems, early death
Hb^AHb^s
1. Carry the sickle cell trait
2. Equal amounts of each type of hemoglobin in your red blood cells
3. rarely suffer symptoms (maybe some sickling and mild symptoms in low oxygen concentrations, like high altitudes)
Who is primarily affected by sickle cell anemia?
1. Africans (and descendants) - 40% of black population has trait
2. Caucasians of Mediterranean descent
Advantage of sickle cell anemia trait in tropical places:
1. The malaria parasite spends part of its life in human's liver and red blood cells and part in mosquitoes
2. If you have sickle cell anemia or the trait, when parasite enters, cell ruptures and kills it before it can reproduce
3. Without malaria, sickle
Sickle cell trait- codominance and incomplete dominance?
1. Codominance because both alleles' products, the types of hemoglobin, are equally expressed
2. Incomplete dominance because they may exhibit some symptoms of the disease (intermediate phenotype)
Polygenic Inheritance
Inheritance of phenotypic traits that depend on many genes acting simultaneously (and these genes all have multiple alleles as well)
Diploid
1. A cell or organism consisting of two sets of chromosomes- usually one set from the mother and one from the father
2. 2n
3. Human's somatic cells have 46 chromosomes
Rediscovering Mendel
1. His work, published in 1865, was "lost" and then "rediscovered" in early 1900s by three separate researchers
2. It was not accepted right away- not until being integrated into Chromosome Theory of Inheritance and then proven by T. H. Morgan's work
3. T
Chromosome Theory of Inheritance
1. Identified chromosomes are the carriers of DNA
2. Genetic mapping- chromosomes are linear structures with genes located at specific sites called loci along them
3. Begun by Sutton and Boveri (1902), but confirmed by Morgan and colleagues (1910), as wel
1953
Watson and Crick discovered the double helix structure of DNA
Thomas Hunt Morgan
1. work at Columbia (with undergrads)
a. his undergrad student, Sturtevant, developed first genetic map
2. Looked at fruit flies
- cross breeding to create mutations
- first widely used model organism
3. Theory of sex-linked inheritance
Sir Archibald Garrod (1902)
1. First formalized paper claim that a human disease, black urine disease (alkaptonuria), has genetic causes
(which he calls "inborn errors of metabolism" from lacking some enzyme)
2. He saw it was being passed through generations in families
3. Paper was
Slide = Fly under the miscroscope
called a physical map
The role of Corn in inheritance
...
The gene for cystic fibrosis was discovered in
1989
- a mutation in this CFTR gene caused CF
- over 1000 mutations have since been identified (1000 alleles described at the locus)
- normally this gene codes for the CFTR protein, which acts as a channel for cells to release chloride and other ions
Gene Therapy for Cystic Fibrosis: Other issues researchers face, beyond simply delivery:
1. Determine lifespan of affected lung cells
2. Identify "parent cells" that produce CFTR cells
3. Find out how long treatment should last
4. Find how much treatment should be repeated
Type of cells used for first cystic fibrosis gene therapy:
Lung Cells
- cells are readily accessible
- lung damage is most common and life-threatening complication for CF patients
- Hopefully, treatments can later be adapted for other organs
Possible treatment for CF: Treating lung infections
1. Researchers at U Washington's Genome Center and PathoGenesis
-Completed genetic map of bacterium P. aeruginosa
3. Bacterium is most common cause of chronic and fatal lung infections in people with CF
4. Hopefully, genetic sequence of it will allow drug
Where are researchers pooling their information about gene expression findings for CF?
Cystic Fibrosis Foundation funds the CF Foundation Therapeutics at U. North Carolina Chapel Hill
Carrier testing for CF
1. Blood or saliva tests to see if some couple is at risk of conceiving a child with CF
2. Not an infallible test
3. If both parents are carriers- they may want to have prenatal testing done
Prenatal testing for CF
1. Around 11th week: chorionic villi sampling (CVS)
- remove small amount of placenta
2. 16th week: amniocentesis
- take amniotic fluid from around baby for testing
3. If test positive
a. terminate pregnancy
b. Prepare to take care of ill child
(no before
Genetic Testing or DNA-based testing
1. Analysis of a person's DNA to determine their risk for a particular health condition or to confirm the diagnosis of genetic disease 2. Becoming more and more available
3. Today, newborns are screened for 21 of 29 serious genetic disorders in all states
Genetic Information Nondiscrimination Act (GINA)
1. Passed in 2008 by US Congress
2. Insurers cannot set higher premiums or deny coverage o healthy people based on genetic test results
3. Illegal for employees to use genetic test results in hiring/firing
4. Does not address other privacy issues though (
Benefits of Genetic Testing
1. Confirm a diagnosis of a genetic disorder before symptoms even appear (early treatment is possible)
2. Rule out likelihood of getting an inherited disorder (soothing)
3. Allow people to make informed reproductive decisions (are they carriers? does thei
Human Pedigree
Like a family tree
blue area is affected
Primary Literature forms the Building Blocks of ....
Knowledge!
Cystic fibrosis transmembrane conductance regulator:
CFTR protein!
1. encoded by CFTR gene
2. When the CFTR gene is mutated (and there are over 1,000 possible mutations), this protein does not function properly and you get cystic fibrosis
3. Part of family of ABC-transporter proteins; a glycoprotein
4. An i
CFTR gene (its structure)
1. On chromosome 7q31
2. 190kb in length = huge
3. Coding region is within about 27 exons
Huntington Disease
1. Progressive nerve degeneration leading to mental and physical disability and death
2. Symptoms appear in 30s
3. Death in 40s-50s
4. Caused by a rare dominant-lethal allele (single gene mutation)
5. Fatal with no known cure, but there is a genetic test
HD (a dominant-lethal allele)
1. the dominant allele that causes Huntington disease
2. This means that even having one HD allele will result in the disease
3. The recessive allele is hd
Why do dominant-lethal alleles tend to eliminate themselves from the population?
1. Usually kill person before reproduction (there are no carriers because everyone with the allele gets the disease)
2. Huntington is different in this regard because symptoms develop later in life
Human Genome Project
Located 22,000 genes on the human genome and identified their functions (allowed us to identify certain genes responsible for many disorders like breast and skin cancer, osteoporosis)
Frequency of Huntington Disease in US and Japan
1. 7/100,000 in US
2. 0.1/100,000 in Japan
A breaking of the gene is...
Loss of Function
Dominant phenotypes tend to be due to ...
and Recessive phenotypes tend to be due to...
Dominant phenotypes- Gain of function mutations
Recessive Phenotypes- Loss of function mutations
Autism spectrum disorders (ASDs)- a group of developmental disorders that includes...
A variety of medical autism diagnoses that vary in severity
Include:
Autistic disorder
Asperger's Syndrome
Pervasive Developmental Disorders (PDD) - a category
Most commonly diagnosed childhood developmental disorder:
Autism
- affects 1 in every 150 US children
- Diagnoses are increasing at a rate of 10 to 17 percent per year
- Incidence is same around the world (no ethnic, racial, or social factors)
- 4 times more common in boys- one of genes linked to autism is fragi
Symptoms of autism
4 Factors to Know: (variations; can have all or some- and having them does not mean you have it)
1. Impaired Social Interaction
2. Problems with Communication (verbal and nonverbal like eye contact)
3. Repetitive Behaviors
4. Limited Activities
(also phys
Hallmark symptom of autism
Usually impaired social interaction
- avoid eye contact
- do not respond to their name
- failure to understand or see social cues (cannot pick up on cues from tone of voice or facial expressions)
How is autism diagnosed?
1. Usually develops before age 3 (most show symptoms in first year of life, but some regress at around 18 months)
2. Usually it is done early by parents or other people- but its hard to diagnose because it varies so widely
3. Standardized testing plus cli
Autism specialists are usually-
psychologists, psychiatrists, developmental pediatricians, pediatric neurologists, or medical geneticists
Diagostic tests for autism include:
1. CARS - Childhood Autism Rating Scale
2. the ABC - Autism Behavior Checklist
3. GARS - Gilliam Autism Rating Scale
Formal diagnosis by an autism specialist usually is done upon completion of the:
1. ADOS - Autism Diagnostic Observation Scale
2. ADI-R - Autism Diagnostic Interview-Revised
3. CHAT
- Checklist for Autism in Toddlers
- used in pediatricians office to screen for symptoms
Cure for autism
There is none - though intensive treatment therapy does help
Treatment for autism
1. Medical, family-centered, educational, and behavioral program to help children with language and social interactions
2. Help children stop repetitive, tantrum, self-harm behaviors
3. Medications to treat certain symptoms (though none are autism specifi
Children with autism make take medications to help with:
Specific symptoms
- self-harm behaviors
- inattention
- poor sleep
- repetitive behaviors
What causes autism?
Scientists are not sure, but probably a mix of genetics and environment
- 85% have iodiopathic autism
- 15% have secondary autism
Idiopathic
Of unknown cause
Secondary autism
1. 15% of cases
2. A single-gene disorder, a chromosome abnormality, or an environmental agent can be identified
3. Includes: Exposure during pregnancy to rubella, valproic acid, and thalidomide (though these may be combined with being genetically predisp
Childhood immunizations and autism:
1. the primary focus in the search for environmental causes of secondary autism
2. Certain vaccines are given around same time that regressive-onset autism is recognized (mercury in thimerosal preservative)
3. No scientific evidence though
Proteome
1. Entire set of proteins in a cell or organism that are expressed by a genome
2. Function in a complex network
Gene mapping
1. It is possible to map the human chromosome
2. Using DNA markers you can illustrate certain genes' locations and distances
3. We can map disease genes
Phenotypic traits governed by polygenic inheritance typically distribute across the human population-
As a continuous range of phenotypes with more people at the middle values (bell-shaped curve)
example- there are a range of possible heights that the many genes influencing height may dictate, but most people will come out as medium height
Diseases caused or influenced by polygenic inheritance:
Cancer, high blood pressure, heart disease, and stroke
Examples of phenotypic traits inherited through polygenic inheritance:
eye color, height, body size
Example of Polygenic Inheritance using height:
Hypothetical:
a. There are three genes influencing height, A, B, and C.
b. Each of these has two alleles (an incomplete dominant tall allele or recessive short allele)
c. Cross 2 people with medium height - Heterozygotes (AaBbCc x AaBbCc)
d. Most offsprin
Our genotype usually does not determine whether we develop a disease phenotype (a heritable disease):
1. Phenotype is also influenced by environment and lifestyle choices
- The environment can influence how genes are expressed as proteins and how they contribute to your phenotype
2. Usually, we only can inherit an increased risk of developing a disease
3.
Linked alleles
Alleles that are often inherited together because they are on same chromosome
1. How often two linked alleles are inherited together is directly proportional to how close they are to each other on a chromosome
2. and inversely proportional to how often cr
Linkage mapping
Scientists ability to map genes' positions based on how often particular linked alleles are inherited together
3 Major Sources of Genetic Variability as a result of sexual variability:
1. Independent assortment of alleles located on different chromosomes
2. Partial shuffling of linked alleles as a result of of crossing-over between autosomes
3. Random fertilization of an egg by a sperm
Karyotype
A composite display of all the chromosomes of an organism (a numbered arrangement)
Chromosomes are identified and paired according to
size, centromere location, and characteristic banding patterns
Are the sex chromosomes a homologous pair?
No!
They do not look alike; they do not match up; they carry different genes and perform different functions as a result
The advantage of having pairs of autosomes:
1. There are two copies of each gene, so there is a backup there to carry out its function in most cases
2. This is what makes males more likely to display any recessive trait on the X chromosome
- They are more susceptible to diseases associated with rec
Association between Genes and Autism
1. Autism can result from the disruption of fetal brain development
2. This is from defective genes
- Defects in genes that control brain growth - Defects in genes that regulate how neurons communicate with each other (Studies suggest people with autism h
The risk for a sibling of an individual who has idiopathic autism of also developing autism is....
Around 4 percent
plus an additional 4 to 6 percent risk for a milder condition that includes language, social or behavioral symptoms.
Note: Brothers have a higher risk (about 7 percent) of developing autism, plus the additional 7 percent risk of milder au
When the cause of autism is a chromosome abnormality or a single-gene alteration, the risk that other brothers and sisters will also have autism depends on:
The specific genetic cause.
Is autism inherited?
1. There are increases in autism in families
2. But individual genes do not describe the entirety of what causes autism