Final Genetics

8/7/2019 Final Genetics

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GENETICSis the science of heredity.

Heredity is the transmission of genetic orphysical traits from parent to offspring.



CHARACTERISTICS

T hese are features youexhibit physically

( your looks)

Example: Eye color - green



TRAITS

The different versions of a

characteristic

Example: blue, green, and

brown eyes



INHERITANCE

´ Occurs when traits are

passed down from

parent to child.



GREGOR MENDEL

* Austrian Monk* Considered the ´Father of Heredityµ* He conducted plant breeding

experiments in their monasterygarden.

* In 1865 he made his work public,units of inheritance.



WHAT MAKES US UNIQUE ?

* Each of the 100 T rillion cells in our bodyexcept the red blood cells contains theentire human genome, in the nucleus ofevery cell is the genetic information

´blueprintµ to construct the individual.

* It is the Deoxyribonucleic acid (DNA)

Function of DNA* Genetic code for almost every organism.

* Provide template for protein synthesis.



GENETIC INFORMATION

´ Gene ² basic unit of geneticinformation. Genes determine theinherited characters.

´

Genome ² the collection ofgenetic information.

´ Chromosomes ² storage units ofgenes.

´́ DNADNA - is a nucleic acid thatcontains the genetic instructionsspecifying the biologicaldevelopment of all cellular formsof life

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BASES OF DNAAdenine= A

Thymine= T

Guanine= GCytosine= C

A always pairs with T

C always pairs with G



BASES OF RNAAdenine= A

Uracil= U

Guanine= GCytosine= C

G always pairs with C

T from the DNA = A in the RNAA from the DNA = U in the RNA



DNA MODEL



�DNA is information

�

DNA replicates in s-phase

� Daughter cells carry

�identical information

� Represented as astring

�over ={A,C,G,T}

� Main agent ofinformation

�transfer acrossgenerations



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�DNA replication

�One ´parentalµ double

stranded DNA molecule totwo identical ´daughterµ

molecules (semiconservative)

� How?

�DNA unwinds and strandsare separated (replication

fork)

� Free nucleotides are

matched to exposed bases� DNA polymerase joins

nucleotides

�New and original strands

rewind



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�Addition of nucleotides

� DNA polymerase

only adds nucleotides to

the 3· end ofDNA

� Synthesis

requires energy(gained from

hydrolysis of

phosphatebonds)



�Central Dogma of Molecular Biology

DNA

í Double-stranded

í Long, immobileí Stable, inert

í Information across

generations

RNA:í Single-stranded

í Short, mobile

í Short-lived, reactive

í Information around

the cell Protein:

í Functional gene product



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�Transcription

1-1 copying of the gene

sequence: ={A,C,G,U} Performed by enzymes

As needed, regulated by

nearby DNA sequences



TRANSCRIPTION

DNA is copied into a complementarystrand of mRNA.

WHY?´ DNA cannot leave the nucleus. Proteins

are made in the cytoplasm. mRNA

serves as a ´messengerµ and carries theprotein building instructions to theribosomes in the cytoplasm.



HOW TRANSCRIPTION OCCURS

1. RNA polymerase untwists and unzips asection of DNA (usually a single gene)from a chromosome.

2. RNA polymerase pairs free RNA nucleotidesto the exposed bases of one of the DNAstrands following base pair rules.

´ Uracil replaces thymine

´ Only 1 strand of DNA serves as a template,the other ´hangs outµ



3. Newly synthesized mRNA separates fromtemplate DNA and DNA zips back up.



TRANSCRIPTION EXAMPLE

´ T ranscribe the following DNA Sequence inmRNA

T AC CGG AT C CT A GGA T CA

AUG GCC UAG GAU CCU AGU



PROTEINS

Structural and functional components of organisms.

´ Composed of amino acids

´ order of nucleotides in DNA determinesorder of amino acids in a protein

´ One gene codes for one protein



DNA: TAC CTT GTG CAT GGG ATC

mRNA

AU

G GAA

CA

C GUA

CCCUA

GA.A MET G.A HIS VAL PRO STOP



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Eukaryotic mRNA

exits the nucleus

Messenger RNA istranscribed inside

the nucleus but

translated outside Requires processing

into mature mRNA



�23

mRNA Processing

Capping head,

Poly-A tail added

Most of the

pre-mRNA is

spliced out



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Translation

Machinery:í Ribosome

í tRNA ádaptorsµ

From mRNA

nucleotide triplets toamino acids

Uses the geneticcode: 4320+µstopµ



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A U G G G C U U A A A G C A G U G C A C G U U

T his is a molecule of messengerRNA.

It was made in the nucleus by

transcription from a DNA molecule.

mRNA

molecule

codon



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A ribosome on the roughendoplasmic reticulum attaches

to the mRNA molecule.

ribosome



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It brings an amino acid to the first

three bases (codon) on the mRNA.

Amino acid

tRNA molecule

anticodon

U A C

A transfer RNA molecule arrives.

T he three unpaired bases (anticodon)on the tRNA link up with the codon.



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A peptide bond formsbetween the two aminoacids.

Peptidebond



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T he first tRNA moleculereleases its amino acid and

moves off into the cytoplasm.



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T he ribosome moves along themRNA to the next codon.



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Another tRNA

molecule brings thenext amino acid intoplace.



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A peptide bond joins thesecond and third amino

acids to form apolypeptide chain.



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T he polypeptide chain gets longer.

T he process continues.

T his continues until a termination(stop) codon is reached.

T he polypeptide is thencomplete.



�34



�35

U C A G

U Phenylalanine Serine Tyrosine Cysteine U

U Phenylalanine Serine Tyrosine Cysteine C

U Leucine Serine Termination Termination A

U Leucine Serine Termination Tryptophan G

C Leucine Proline istidine Arginine U

C Leucine Proline Histidine Arginine C

C Leucine Proline Glutamine Arginine A

C Leucine Proline Glutamine Arginine G

A Isoleucine Threonine Asparagine Serine U

A Isoleucine Threonine Asparagine Serine C

A Isoleucine Threonine Lysine Arginine AA Methionine Threonine Lysine Arginine G

G Valine Alanine Aspartic acid Glycine U

G Valine Alanine Aspartic acid Glycine C

G Valine Alanine Glutamic acid Glycine A

G Valine Alanine Glutamic acid Glycine G

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st

b

a

s

e

3rd

b

a

s

e

THE GENETIC CODE

2n base



´ DNA replication ² starts with the separation of DNAstrands. T hen enzymes use each strand as a template to

assemble new nucleotides into a complementary strand.Using the enzyme DNA polymerase, the cell synthesizesone daughter strand as a continuous piece, the other as aseries of shirt pieces which are then connected by theenzyme DNA ligase

´ Codons- triplets of bases

´ T ranscription ² in the nucleus, the DNA helix

unzips, and RNA nucleotides line up and hydrogen-bondalong one strand of the DNA, following the base-pairingrules.

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´ As the single-stranded messenger RNA (mRNA)peels

away from the gene, the DNA strands rejoin. EukaryoticRNA is processed before leaving the nucleus as mRNA.Noncoding segments called introns are spliced out, and acap and tail are added to the ends.

´ Translation ²takes place in the cytoplasm. A ribosomeattaches to the mRNA and translates its message into a

specific polypeptide, aided by transfer RNAs (tRNAs)that act as interpreters. Each tRNAis a folded moleculebearing a base triplet called as anticodon on one end; a

specific amino acid is added to the other end.

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CHROMOSOMES

The DNA in every cell is located in rod like

segments called chromosomes

Chromosomes occurs in pairs in every cell of our

body except in the sperm and ovum.

Chromosomes numbers are the same for each

specie.



CHROMOSOME NUMBERS

Species Diploid # Haploid #

Cattle 60 30

Swine 38 19Sheep 54 27

Horse 64 32

Human 46 23

Chicken 78 39

Goat 60 30

Donkey 62 31



CHROMOSOMES

´ There are 2 sex chromosomes included inthe diploid number of the chromosomes.

´ All of the other chromosomes are referredto as autosomes.

´ In mammals if the sex chromosomes arealike, XX it results in a female.

´ If the sex chromosomes are different, XY it results in a male.



CHROMOSOME LOGICALSTRUCTURE

´ Locus ² location of a gene/markeron the chromosome.

´

Allele ² one variant form of agene/marker at a particular locus .

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Locus1

Possible Alleles: A1,A2

Locus2Possible Alleles: B1,B2,B3



SEX DETERMINATION´ Females contribute an X chromosome towards the sex

of their offspring.

´ Males can contribute an X or a Y chromosome toward

the sex of their offspring.´ Absence of an Y chromosome results in a the embryo

developing into a female.

´ Presence of an Y chromosome results in the embryo

developing into a male.



SEX DETERMINATION

´ Gametogenesis =

Formation of gametes

through meiosis.´ Male = 4 viable

spermatids

´ Female = 1 viable

ovum, 3 polar bodies.



HUMAN GENOME

Most human cellscontain 46 chromosomes:

´ 2 sex chromosomes (X,Y):XY ² in males.XX ² in females.

´ 22 pairs of chromosomesnamed autosomes.

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GENOTYPES PHENOTYPES

Át each locus (except for sex chromosomes)there are 2 genes. T hese constitute theindividual·s geno type at the locus.

´T he expression of a genotype is termed a

p heno typ e . For example, hair color, weight,or the presence or absence of a disease.

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GENOTYPES PHENOTYPES (EXAMPLE)

´ Eb- d om inan t allele.

´ Ew- r ecess iv e allele.

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genotypes

phenotypes



DOMINANT VS. RECESSIVE

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� A d om inan t allele isexpressed even if it is

paired with a recessiveallele.

�A r ecess iv e allele is

only visible when pairedwith another recessiveallele.



ONE LOCUS INHERITANCE

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heterozygote homozygote

21A | A a | a

A | a 3 4 a | a

A | a 5 6 a | a

Male

Female



MENDEL·S 1ST LAW

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T wo members of a gene pair segregate from each other into

the gametes, so half the gametes carry one member of the

pair and the other half carry the other member of the pair.

Y / y y / y

½ y/y

½ Y/y

½ y

½ Y

all yGamete

production

Gamete

production



CALCULATING PROBABILITIES

´ We want to predictpatterns of inheritanceof traits and diseases in

pedigrees.

´ E.g., we want to knowthe likelihood that a

dog chosen at randomfrom the studypopulation will have blueeyes.

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PUNNET SQUARE

´ Angus- Black coat color is dominant.

´ BB = Homozygous Dominant and Black

´ Bb = Heterozygous and is black

´ bb = Homozygous recessive and red

´ A heterozygous bull is mated to 50 homozygous

recessive cows.

´ How many calves are black?

´ How many calves are red?

´ What is the genotypic and phenotypic ratios?



PUNNET SQUARE

B b

b

b

Bb bb

Bb bb



RESULTS

´ 2 heterozygous = Bb

´ 2 HomozygousRecessive bb

´ 25 Black, 25 Red

´ Genotypic ratio = 0:2:2

´ Phenotypic ratio =

2 Black: 2 Red



WHAT ARE SEX LINKED GENES?

´ Some recessive genes are attached to the X

and Y chromosomes

´ Humans: Colorblindness and Baldness are onthe X chromosomes

´ In Men, traits expressed anytime present

´ In Women, must have two recessives to show

trait

´ Children get baldness from mothers



IF DAD IS BALD,WILL YOU BE

BALD?

X Y

X XX X Y

XX XYX

B

B

B



BALDNESS IS CARRIED BY THE

MOTHER

X Y

X XX X Y

XX XYX

BB B



WHAT IF MOM IS BALD?

X Y

X XX X Y

XX XYX

BB B

B B B



WHAT IS INCOMPLETE

DOMINANCE

?´ If both genes express themselves

´ Shorthorn Cattle: Red male mated to a White

female = Roan calf

´ RR crossed rr = Rr



PUNNET SQUARE

´ Shorthorn Cattle

´ RR = Red

´

rr = white´ Rr = roan

´ If a red bull (RR) is mated to a white cow (rr),

what color will the calves be?



SHORTHORN: RED XWHITE

R R

r

r

Rr Rr

Rr Rr



PUNNET SQUARE

´ If a red bull (RR) is mated to a roan (Rr) cow,

what color will the calves be?



SHORTHORN: RED X ROAN

R R

R

r

RR RR

Rr Rr



WHAT IF BOTH PARENTS ARE ROAN?

R r

R

r

RR Rr

Rr rr

X li k d I h i



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X-linked Inheritance

Different results obtainedfrom reciprocal crossesbetween red-eyed andwhite-eyed Drosophila.

: T he geneExplanationresponsible for eye-coloris X-linked. Females have

2 X-chromosomes, whilemales have 1 X-chromosomeand 1 Y-chromosome.



MENDEL·S 2ND LAW

´ Different gene pairs assort independentlyin gamete formation.

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Gene pairs on SEPARATE CHROMOSOMESassort independently at meiosis.

T is ´la µ is tr e only in some ases.



MEDICAL GENETICS

When studying rare disorders, 6 general patternsof inheritance are observed:

´ Autosomal recessive´

Autosomal dominant´ X-linked recessive´ X-linked dominant´ Codominant

´

Mitochondrial

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MEDICAL GENETICS (CONT.)

Autosomal recessive

´ T he disease appears

in male and femalechildren ofunaffected parents.

´ e.g., cystic fibrosis

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Autosomal dominant

´ Affected males andfemales appear in eachgeneration of thepedigree.

´ Affected mothers andfathers transmit the

phenotype to both sonsand daughters.

´ e.g., Huntington disease.

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X-linked recessive

´ Many more males thanfemales show the disorder.

´ All the daughters of anaffected male arećarriersµ.

´ None of the sons of anaffected male show the

disorder or are carriers.´ e.g., hemophilia

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X-linked dominant

´ Affected males pass thedisorder to all daughters

but to none of their sons.´ Affected heterozygous

females married tounaffected males pass thecondition to half their sons

and daughters´ e.g. fragile X syndrome

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Codominant inheritance

´ T wo different versions(alleles) of a gene can beexpressed, and eachversion makes a slightlydifferent protein

´ Both alleles influence thegenetic trait or determinethe characteristics of the

genetic condition.´ E.g. ABO locus

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Mitochondrial inheritance´ T his type of inheritance

applies to genes inmitochondrial DNA

´ Mitochondrial disorderscan appear in everygeneration of a family andcan affect both males andfemales, but fathers do notpass mitochondrial traitsto their children.

´ E.g. Leber's hereditaryoptic neuropathy (LHON)

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QUESTION #1



QUESTION #1

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1 2

� Write the genotypes in every possible place.� If individuals 1 and 2 marry, what is the probability thattheir first child will be sick?



QUESTION #2

´

PKU is a human hereditary disease resulting frominability of the body to process the chemicalphenylalanine (contained in protein that we eat).

´ It is caused by a recessive allele with simple Mendelian

inheritance.

´ Some couple wants to have children. T he man has asister with PKU and the woman has a brother with PKU.T here are no other known cases in their families.

´ What is the probability that their first child willhave PKU ?

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QUESTION #2 SOLUTION



QUESTION #2-SOLUTIONHIGHLIGHTS

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P/p P/p P/p P/p

p/p p/pP/- P/-

P ² the normal allelep ² the mutant allele

QUESTION #3



QUESTION #3

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1 2 3 4 5 6 7 8 9 10

a. What is the most likely mode of inheritance ?

b. What would be the outcomes of the cousin marriages1 x 9, 1 x 4, 2 x 3, and 2 x 8 ?

� T

he disease israre

.

QUESTION #3 SOLUTION



QUESTION #3-SOLUTIONHIGHLIGHTS

a. Observations:« After the disease is introduced into the family in generation

#2, it appears in every generation dominant!« Fathers do not transmit the phenotype to their sons

X-linked!

b. T he outcomes:« 1 x 9: 1 must be A/a

9 must be A/Y« 1 x 4: 1 must be A/a

4 must be a/Y« 2 x 3: 2 must be a/Y

3 must be A/a« 2 x 8: 2 must be a/Y

8 must be a/a

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Same

All normal



NOTES

´ Cystic fibrosis ² disease affecting the mucus lining of the

lungs, leading to breathing problems and other difficulties

´ Huntington disease - or Huntington's chorea is an inherited

disorder characterized by abnormal body movements called

chorea, and loss of memory. There also is evidence thatdoctors as far back as the Middle Ages knew of this devastating disease. The incidence is 5 to 8 per 100,000. It takes its namefrom the New York physician George Huntington who firstdescribed it precisely in 1872.

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NOTES

´ Hemophilia-illness that impair the body's ability tocontrol bleeding.

´ Fragile X syndrome - is a genetic condition thatcauses a range of developmental problems including

learning disabilities and mental retardation. Usuallymales are more severely affected by this disorder thanfemales. In addition to learning difficulties, affectedmales tend to be restless, fidgety, and inattentive.Affected males also have characteristic physical

features that become more apparent with age.

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NOTES -CONT

´ DNA - a pair of molecules joined by hydrogen bonds: it is organizedas two complementary strands, head-to-toe, with the hydrogenbonds between them. Each strand of DNA is a chain of chemical"building blocks", called nucleotides, of which there are fourtypes:adenide (abbreviated A), cytozyne (C), guanine (G) andthymine (T ).

´ Mitochondria, which are structures in each cell that convertmolecules into energy, each contain a small amount of DNA.

´ A chromatid forms one part of a chromosome after it has coalescedfor the process of mitosis or meiosis. During either process, the

word "chromosome" indicates a pair of two exactly identical("sister") chromatids joined at the central point of each chromatid,called the centromere.

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NOTES -CONT

´ Mitosis is the process by which a cell separates itsduplicated genome into two identical halves

´ Meiosis is the process that transforms one diploidinto four haploid cells.

´ Reciprocal cross a cross, with the phenotype of each sex reversed as compared with the originalcross, to test the role of parental sex on inheritancepattern. A pair of crosses of the type genotypeA(female) X genotype B(male) and genotype B(female)

X genotype A(male).

Final Genetics

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