Genetics

• • • Gregor Mendel-Father of Genetics Born-1822 in Austria Entered the monastery at age 21. After failing the exam to be a teacher he went to study at the University of Vienna. There he studied with some important scientists of his day.

1857-Mendel began breeding peas in the abbey gardens.

– Why was choosing peas so important?

• Traits show as “either/or” • Had control over mating (they normally self-fertilize) • He began with true breeding plants

• • • P = parent generation F 1 F 2 = first generation (first filial) = second generation (second filial) • Sample cross: – P purple x white flowers – – F F 2 1 all purple flowers ¾ purple, ¼ white – Mendel reasoned the white trait was not gone in the F 1 but was being masked by the more dominant purple trait

• Mendel’s law of segregation: – The 2 alleles separate during gamete formation – Each parent has 2 copies of every gene. When forming the sex cells only one copy goes into each cell.

If Mom has DD--------eggs all have D If Dad has dd----------sperm all have d

• A test for the law of segregation: – Purple x white P: F1: F2: PP x pp Pp x Pp 1PP: 2Pp: 1pp *The fact that the white appears again proves that the alleles have to separate from each other.

• Vocabulary: – Trait-varieties of alleles (purple or white) – Homozygous-alleles are the same, (may be either dominant or recessive-PP, pp, TT, tt) – Heterozygous-alleles are different—Pp, Tt

– Phenotype-appearance, traits that are visible – Genotype-actual genes present

• Test cross: – Done to determine if genes are homozygous or heterozygous dominant.

• A dominant parent can be either PP or Pp • Cross with a plant of known genes (pp) – – If all offspring are purple then parent was PP If some offspring are white and some are purple then parent was Pp

• Mendel’s Law of Independent Assortment – From single trait crosses Mendel knew yellow seed were dominant over green seeds and round were dominant over wrinkled. What would happen to theses genes when crossed together?

• • If Y and R stay together then the ratio in offspring would be 3:1 Actual ratio is 9:3:3:1. This means that the 2 genes travel independently of each other to gametes

Probability and genetics

• Probability-the chance an event will occur – An event certain to occur has a probability of 1 – An event certain not to occur has a probability of 0 – Probabilities of all outcomes must add up to 1

• Rule of multiplication: – Use when each occurrence is a separate event – Example: what is the chance of getting heads on 2 coins tossed simultaneously?

• The two coins are separate events.

probability of heads on 1 st coin = ½ probability of heads on 2 nd coin = ½ probability of heads on both is ½ x ½ = ¼

• What is the chance of getting white flowers?

– Chance of egg having p allele is ½ – Chance of sperm having p allele is ½ – ½ x ½ = ¼

• Rule of addition: – Probability an event can occur in 2 or more ways is the sum of each one separate probability.

• Example: what is the probability an F2 plant will be heterozygous from a monohybrid cross?

• Two out of 4 are heterozygous P p ¼ + ¼ = ½ P PP Pp p Pp pp

Monohybrid and dihybrid crosses

• Monohybrid – one trait is crossed at a time Punnett square-device for predicting results of a cross recessive trait is written with a small letter dominant trait is written with a capital letter

• Examples: Trait = seed shape Genes: round = R, wrinkled = r R R R R r R G= P= r r G= P= R r R G= P= r

• • Dihybrid –two traits crossed together First determine the possible combinations of genes: – YyRr = YR, Yr, yR, yr – Yyrr = Yr, Yr, yr, yr

G = P = YR Yr Yr YYRr YYrr Yr YYRr YYrr yR yr YyRr Yyrr YyRr Yyrr yr YyRr Yyrr yyRr yyrr yr YyRr Yyrr yyRr yyrr

Inheritance patterns:

1. Incomplete dominance-the appearance of the F1 is a blend of the parents – Example-snapdragons – P red x white – F1 – F2 all pink ¼ red: ½ pink: ¼ white

• Example: sickle cell anemia – Mutated gene for hemoglobin – Normal genes: Hb A Hb A – – Sickle cell trait: Hb A Hb Sickle cell disease: Hb S S Hb S A person with sickle cell trait produces both normal and sickle cells, a person with the disease makes only sickle cells. They rupture easily, clog arteries, cells don’t get oxygen delivered.

2. Pleiotropy-the expression of one gene can effect many organs or systems (pleio is Greek for more) – – Sickle cell Marfan syndrome-tall body, long arms, nearsighted, weak aorta wall (President Lincoln?) – Cystic fibrosis

3. Co-dominance-both phenotypes are expressed at the same time – – – – – Example one –the four human blood types are a result of 3 genes I A I B i A and B are both dominant genes A = I B = I O = ii A B AB = I I I A B A I B or I or I A B i i Example two-roan cows -- red and white are equal

4. Multiple alleles-three or more alleles of a gene in a population – Example-blood type (3 genes determine 4 blood types) – Example-rabbit fur color • Agouti-gray and yellow (A) • Chinchilla-black and white (a-ch) • Himalayan-white with black extremities (a-h) • Albino-white (a)

5. Polygenic inheritance-many genes contribute to the trait, creates an additive effect – Example: human skin color AABBCCDD is darkest, aabbccdd is lightest. – Other examples are height, weight, eye color

6. Epistasis-one gene alters or interferes with the expression of another.

– Example-fur color in many mammals.

In mice black hair is dominant to brown.

black – B brown – b A second gene determines how much color is deposited in the hair.

C—mouse will be black or brown c—mouse will be white *even if the mouse has BB for black hair, if the other genes are cc for no color, the mouse will not show the black fur trait.

• • Environmental effects some alleles are temperature sensitive.

Examples: arctic foxes, Himalayan rabbits, Siamese cats

Some alleles are pH sensitive Example: hydrangeas

Locating genes on chromosomes: • The first evidence that showed certain genes were located on a specific chromosome came from Thomas Morgan.

– – He chose fruit flies to work with Using eye color as the trait • • Females had red eyes (wild) Males had white (mutant)

• • In his crosses he found that the white eye color was linked to the sex of the fly. He determined that this meant the gene was on the sex chromosome.

Sex linked traits

• Remember that humans have 23 pairs of chromosomes. Of those, 22 pairs are autosomes and 1 pair are sex chromosomes.

– Male sex chromosomes = XY – Female sex chromosomes = XX – Gender of the offspring is determined by the male and is a 50/50 chance

female (XX) male (XY) eggs X X X Y x x X XX XY X XX XY sperm Y X

Sex Determination in other animals

• Not all animals determine gender like humans.

– Grasshoppers have only 1 sex chromosome • Females are XX, males are X – Birds and some fish the female determines the sex of offspring • Females are ZW, males are ZZ – Bees and ants don’t have sex chromosomes • Females come from fertilized eggs (they are 2n) • Males come from unfertilized eggs (they are n)

Dosage compensation

• Probably occurs to make females and males equivalent in X’s, one X chromosome in a female becomes inactive

• Inactive X condenses into a compact unit and is pushed to the side. It is called a Barr body. Which X becomes Barr body is random. Females end up as a mosaic—some cells have active X from mom and others have active X from dad.

– Examples • Calico cat • Female sweat glands

Examples of sex linked traits • X linked recessive-show up in males more often – Hemophilia-blood clotting disorder, ran through royal families in Europe – Dushenne Muscular Dystrophy-muscles atrophy, are replaced by fat tissue during ages of 2 and 10. Typically die in early 20’s

– Red green color blindness-can’t distinguish between those two colors

• X linked dominant-rare, few examples – Faulty enamel trait-the hard enamel on teeth fails to develop correctly

• Y linked dominant-few traits are on the Y other than male traits. It is questionable if these traits exist

Chromosome abnormalities

• Chromosome abnormalities may be caused by a change in number or a change in the structure of the chromosome.

Changes in chromosome number: • Nondisjunction-homologous chromosomes do not separate correctly during meiosis. One gamete receives an extra copy, other receives none. This creates: – Polyploidy-entire sets of chromosomes may be added – Aneuploidy-whole chromosomes are lost or gained

Nondisjunction in sex chromosomes

• 45 XO – Turner’s syndrome – 1 in 5000 female births – Short stature, barrel chest, thick neck with webbing, normal intelligence but may have learning disabilities, often has heart problems, no Barr bodies, sterile

• 47 XXX – triple X – Sex- female – Usually fertile, fairly normal – One X will remain functional and the other two become Barr bodies • 47 XXY – Klinefelter’s – Sex- male – Unusually tall, extra X becomes Barr body, usually sterile, may show breast development

• 45 OY - never develops • 47 XYY – Supermale (Jacob’s syndrome) – Unusually tall, severe acne, not well coordinated, emotionally unstable.

Nondisjunction in autosomes

• • Humans who have lost a copy of an autosome do not survive.

Most who inherit an extra copy also do not survive except for 5 of the smaller chromosomes: 13, 15, 18, 21, 22

• Trisomy 21 and 22 usually survive to adulthood. They are usually short and have poor muscle tone. They always have some mental deficiency.

• Trisomy 21- Down’s syndrome – One in 750 births – 97% have three 21 chromosomes, 3% have 2 plus a portion of another – Nearly always related to mother’s age.

• • At age 20 it is a 1 in 1700 chance At age 45 it is a 1 in 16 chance – Symptoms include: short stature, heart defects, mental deficiency, shorter lifespan, most are sterile, slanted eyes, hand fold, large tongue

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

• Trisomy 18, 13 and 15 all cause severe developmental defects and infants will die within a few months.

Changes in structure:

• Deletion-section of chromosome broken off and lost – Example: Cri-du-Chat “cat cry syndrome” • Deletion on chromosome 5 • Mental deficiency, cry like a cat, usually die in early infancy – Example: Prader-Willi syndrome • • Deletion on chromosome 15 from Dad Mental deficiency, obesity, short – Example: Angelman syndrome • • Deletion on chromosome 15 from mom Jerky movements, uncontrollable laughter

• Duplication- occurs at crossing over, part of a chromosome is copied twice • Translocation-part of a chromosome breaks off and reattaches to another chromosome

• Fragile X-tip of X chromosome hangs by a thin thread of DNA – Males- 1 in 1500 births – Females- 1 in 2500 births – Most common form of mental deficiency – Children are often hyperactive or autistic, adults have protruding ears, short stature, long face and prominent jaw

Autosomal recessive disorders

• PKU- phenylketonuria – Missing an enzyme to break down phenylalanine, corrected by diet, causes deficency.

– Newborns automatically screened at birth

• Cystic fibrosis – Body cells secrete excess mucus that clogs the lungs, currently they may live into 20’s.

– 1 in 20 in U.S. are carriers

• Tay Sachs – – Blindness, mental deficiency, death usually occurs by age 5 Gene common among Ashkenazi Jews – Caused by a nonfunctional enzyme needed to break down lipids.

Autosomal dominant disorders

• Huntington’s – chromosome #4 has too many repetitions of CAG on the end – – – (11-34 is normal) symptoms begin around age 40 Uncontrollable muscle spasms, personality changes, insanity Affects 1 in 20,000 people

• Progeria – Rapid aging (7-8 times normal rate) – Don’t live to reproduce (spontaneous mutation) • Achondroplasia – dwarfism

• polydactyly

Diagnosis and counseling

• • The likelihood of passing on recessive genes can be determined by using a pedigree chart.

High risk pregnancies often occur when the mother is more than 35 years old.

• Amniocentesis-permits prenatal diagnosis – Withdrawing fluid from around baby to test cells. There is a small danger to offspring.

• Ultrasound – Using sound waves to produce a picture of baby – Cannot see chromosomes but can see if major abnormalities are present, the sex of the child and developmental age by its size

• CVS-less invasive of a procedure – Takes a sample from the chorion which is a membrane that surrounds the placenta – It can be done earlier in the pregnancy and gives rapid results.

• Pedigree chart – Shows genetic connections – Follows a trait through a family

Gene mapping, linkage, crossing over

• Crossing over – Occurs during prophase I – Two homologous chromosomes break and – exchange pieces.

The outcome is genetic variation

• Crossing over can be used to create a genetic map which measures the distance between genes based on the frequency of recombination.

• The distance between any two linked genes is expressed in map units. – One map unit corresponds to an expected crossover frequency of 1% – So, 20 map units has a crossover frequency of 20 %

A little genetics humor…..

• Inbred cat

Picture credits

               http://www.beekeeping.com/biove/bee.jpg

http://www.ento.vt.edu/~idlab/ornimages/grasshopper/grasshopper.jpg

http://www.mayoclinic.org/marfan/images/symptom1.jpg

http://medimages.healthopedia.com/large/marfans-syndrome.jpg

http://www.blc.arizona.edu/courses/181summer/graphics/graphics%20lect11/Life7e-Fig-10-13 0%20incomplete%20dominance.jpg

http://www.ob-ultrasound.net/images/transducer_abdomen.jpg

http://fig.cox.miami.edu/Faculty/Dana/amniocentesis.jpg

http://imgen.bcm.tmc.edu/IPIF/9181.jpg

http://www.accessexcellence.org/RC/VL/GG/images/polydactyly.gif

http://www.mun.ca/biology/scarr/Human_Achondroplasia.gif

http://www.ndpteachers.org/perit/mendel.GIF

http://www.anselm.edu/homepage/jpitocch/genbio/peachar.JPG

http://www.umuc.edu/ade/images/colorblind_compare2.jpg

http://www.perret-optic.ch/optometrie/Vision_des_couleurs/Vis_couleur_images/Color6.jpg

http://www.bbc.co.uk/schools/gcsebitesize/biology/variationandinheritance/0dnaandgenesrev5.sht

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