genetics part i mendel - university of california, san...

•Genetics Part I – MendelInheritable UNITS

Law of SegregationLaw of independent assortment

•Genetics Part II – MorganChromasomal Theory of Inheritance

Sex linked Genes

lecture 13 - May 17thlecture 14 - May 19th

Genetics- Part I

•Mendelian Genetics•The proof for the “particulate” hypothesis (parents pass discrete inheritable units -Genes– that retain their separate identities in the offspring)

•Law of segregation

•Law of independent assortment

•Probability and mendelian inheritance

•Beyond Mendel – understanding inheritance patterns that are more complex than simple mendelian predictions.

•Dominance, multiple alleles, pleiotropy – effects on a alleles of a single gene

•Extending Mendelian genetics for two or more genes

•Genetic Inheritance in Humans


Genetics – Understanding the Genome

•What is a genome?

•Genome = 1n = 1 set of all the chromosomes

•Gene = all the DNA needed to make 1 protein or RNA•Includes DNA which codes for RNA/Protein

•Includes regulatory DNA (where and when the gene will be expressed)

•Comparing Genomes

•Yeast 16 chromosomes 12 million base pairs (BP) ~6000 genes

•Fruit Fly 4 chromosomes 117 million (BP) ~13,600 genes

•Humans 23 chromosomes 3 billion (BP) ~35,000 genes


•Locus: position of a gene on a chromosomes (loci = plural)

•Alleles: variations at a locus

Gene A: A, a 2 alleles of gene A

Genetics: “Following alleles at different loci from generation to generation”

Genetics – Terminology of Genes and Genetics

A

B

C

a

b

c

M P•Maternal and Paternal contribution

Telomere

Centromere


Genetics – Understanding Alleles

•Multiple Alleles can exist for 1 locus

•ALL diploid organisms have at least 2 alleles

•Genotype: List of alleles (Aa Bb, etc)

•Phenotype: Expression of alleles “traits” – what you observe

A, a, a*

Homozygous: alleles are the same

Heterozygous: alleles are different

Dominant allele: one that is fully expressed in phenotype when heterozygous

Recessive allele: hidden allele when heterozygous


Genetics – Genotype vs. Phenotype

A = wild type (normal dominant) : RED eyesa = recessive : White eyesa*= mutant (dominant to all) : ORANGE eyes

AA Aa Aa* aa aa* a*a*

•6 genotypes•3 phenotypes

•Use a punnett square to figure out genotype of progeny:•Male orange eyes Aa* A, a*•Female orange eyes aa* a, a*


Genetics – Punnett Squares

•Use a punnett square to figure out genotype of progeny:

•Example•Male orange eyes Aa* A, a*•Female orange eyes aa* a, a*

a a*

A

a*

4 genotypes in progeny


Genetics – Intro to Mendel

•Two hypothesis•Blending hypothesis: progeny is a mixture of both parents

•Particulate Hypothesis: heritable units

•Mendel’s Garden•Sweet Pea

•Lots of normal variations•Self pollinates

•True breeding plants: all progeny looked the same from generation to generation

•HOMOZYGOUS

•Heritable Traits “characteristics”: Genes (DNA)•Example:

•Flower color purple or white•Seed color yellow or green


Genetics – Intro to Mendel

•Mendel’s Method•Self pollination: leave individual plants alone – wait – seeds - plants

•Planned mating: take pollen from one plant and apply to another

“Genetic Cross”

Following the generations

•P : Parents

•F1 : results of the first cross (between parents)

•F1 : results of the second cross (F1 self pollinate usually)

seeds phenotype

plant

Flowers phenotype


Genetics : Mendel

•Mendel’s genetic cross

•P Purple X White (true breeding)

•F1 100% Purple

•F2 3 Purple : 1 White

P p

P

p

Dominate : PP pp : recessive

Pp : heteozygous

Self-pollinate

cross


Genetics – Law of Segregation

1. Different alleles account for different phenotypes

2. Plants are diploid. Their gametes are haploid. Each plant inherits 1 allele from each parent plant.

3. Alleles can be dominate or recessive

4. For a given heritable factor (gene) – 2 alleles – they segregate during gamete production (Meiosis)! 1 allele per gamete


Genetics – 3 Rules for Mendel’s Genetic Crosses

Rule 1) 2 Plants: true breeding (homozygous)

cross

If different alleles at 1 locus (gene)

F1 will tell which allele is dominant!

Rule 2) If 2 alleles at 1 locus

F1 (heterozygous) self-pollinate : Always see 3:1(Dominate : Recessive)

Rule 3) If you don’t know the genotype of a plant: and “unknown”Mate it to a plant where you DO know the genotype

Purple?PP or Pp?

Mate to a pp (white) (TESTCROSS)


Genetics – TESTCROSSS = smooth

seedss = recessive

wrinkly

?

To determine iffor smooth trait:

Cross to a homozygous recessive

If 100% Smooth – than genotype of unknown SS

If 50:50 Smooth:Wrinkly –than genotype of unknown Ss


Genetics: 1 Gene vs. 2 Genes

Monohybrids: heterozygous for one trait (Pp) – 1 loci (gene) with at least 2 alleles

Dihybrid: heterozygous 2 traits (YyRr)- 2 loci (genes) with at least 2 alleles each

A a

B b A aB b

Chromosome I II I

meiosis

Gametes

meiosis

Gametes

AB, Ab, aB, ab AB or ab

Unlinked Genes Linked Genes

P F1


Genetics: Linked vs. Unlinked Genes

YR

Seed color: Yellow GreenY y

“ Shape: Round WrinkledR r

Mate YYRR x yyrr (true breeding) F1 YyRr F2

Unlinked Genes vs. Linked Genes ?

YR

yr

YR

yr

YYRR YyRr

yyrrYyRr

YR yr

Dihybrid


Genetics: Law of Independent AssortmentOf Unlinked Genes

YR, Yr, rY, ry – four choices (Punnett square = 16 genotypes)

Unlinked Genes

YrR

r

Genes on 2 different chromosomes

F1 progeny

meiosisGametes

Yellow Round : 9Yellow green : 3Yellow wrinkled : 3Green wrinkled : 1

4 Phenotypes (9:3:3:1)


Figure 15.2: Mendel’s Laws – example specific for unlinked genes

All F1 all yellow-round seeds

(YyRr)

F1 Generation(self fertilization)

LAW OF SEGREGATION

LAW OF INDEPENDENT ASSORTMENT

F2 Generation(self fertilization)

Starting with 2 true breeding plants

Gametes

14

14

14

14

YR yr yr yR

Gametes

YRRY

y

rr

y

R Y y r

Ry

Yr

Ry

Yr

R

Y

r

y

r R

Y y

R

Y

r

y

R

Y

YR R

Y

r

y

r

y

R

y

r

Y

rY

r

Y

rY

Ry

R

y

R

y

r

Y

Yellow-roundseeds (YYRR)

Green-wrinkledseeds (yyrr)

P GenerationTwo equallyprobable

arrangementsof chromosomesat metaphase I

Metaphase I

Anaphase I

Metaphase II

9 :3 :3 :1

Ratio9:3:3:1

For unlinked genes


Genetics – Beyond MendelComplex Inheritance Patterns

Dominance and phenotypic expression

Dominant allele: one that is fully expressed in phenotype when heterozygous

Exceptions:Incomplete Dominance: phenotype in between two parents

Co-dominance: both alleles affect the phenotype in separate and distinguishable ways



Incomplete Dominance

White (rr) x Red (RR) Pink (Rr)

RR Red: 100% Red pigment

rr white: No pigment

Rr Pink: ~ half normal red pigment (Pink)

All F1 will be Rr : Pink

This ex: 1 locus (gene); 2 alleles!

R

r

R r



Human Blood Type Co-dominant inheritance at a single gene with two dominant alleles!

Gene involved Sugar transferase:

Sugars (carbohydrates): A-type and B-type sugars added to transmembrane proteins on red blood cells (immune recognition – SELF or NON-SELF)

3 alleles total IA (dom.), IB (dom.), i (rec.)

IAIA IAi IBIB IBi IAIB i i

ABO Blood groups (4 phenotypes expressed)OO No Proteins made

AA OA Only A protein made (B Foreign)BB OB Only B proteins made (A foreign)

AB Both A and B proteins made

O

Universal donor

ABA B



Multiple gene phenotypes and Epistasis

• More than one gene give rise to a single phenotypee.g. skin color, eye colorpolygenic inheritance

Example: Genes in the pathway of A, B, and C all effect skin color

Which comes first in a pathway (EPISTATIC to all others)

A B CEnz. 1 Enz. 2

White(no pigment)

Brown Black

Epistasis: gene at one locus alters the phenotype of the gene at another locus

Mutate Enz 2: Brown mouseMutate Enz 1: White “Mutate Enz1 and 2: White “

Epistasis: method to determine which gene comes 1st in a pathway


1 gene more than (>) 1 phenotype – HOW?

Gene regulator


Example: A protein (Transcription factors) which regulate the expression of multiple genes


Genetics – Morgan’s Chromosomal Theory of Inheritance

•1st to Attribute the idea of a “gene” to a chromosome

•Fruit Fly Drosophila melanogaster

•Very easy to grow•100’s of young from a single fly

•4 chromosomes

•3 autosomes•1 X or Y

•Traits that are not essential for life•Eye color•Body color•Wing shape

XX =

XY =



1st mutant was a male which had WHITE eyes Fly Genetic NotationUses lower case letters:w+ = wild type (normal)w = mutant

XwY = white eye recessive mutant

Xw+Xw+= red eye dominant wild type (normal)

X crossed

F1 was 100% red eyesXw+

Xw Y

But what about the F2 progeny: F1 x F1 ?


P p

P

p

PP Pp

Pp pppurple purple

whitepurple

Remember Mendel’s F1 x F1 (where he was following 1 locus

- 2 alleles – 1 dom, 1 rec)

F2 generation gave 3:1 ratio Purple to white flowers

w+ w

w+

w

w+w+

w+w wwred red

whitered

w+w

Morgan’s F1 x F1 produced similar result

F2 generation gave 3:1 ratio red to white eyes

One major difference?


Xw+

Xw+ Y

Xw


When Morgan crossed the F1 x F1

Conclusion: eye color gene located on X chromosome!!!

See Fig. 15.4


How to identify a sex-linked gene!

Clue #1 if X-linked, recessive disease is most commonly seen in males!

only see in females if homzygous XrXr(r = random mutation) rare!

Clue #2 TEST cross!

a)

b)

XrYmutant males

XRXR

normal femalesx XRY

normal malesXRXr

Heterozygousfemales

XRYnormal males

XrXr

mutant femalesx XrY

mutant malesXRXr

Heterozygousfemales

But if not sex linked RR x rr 100% Rr


Figure 15.5

Double mutant(black body,vestigial wings)


Wild type(gray body,

normal wings)

P Generation(homozygous)

b+ b+ vg+ vg+

x

b b vg vg

F1 dihybrid(wild type)(gray body, normal wings)

b+ b vg+ vg

b b vg vg

TESTCROSS

x

b+vg+ b vg b+ vg b vg+

b vg

b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg

965Wild type

(gray-normal)

944Black-

vestigial

206Gray-

vestigial

185Black-normal

Sperm

Parental-typeoffspring

Recombinant (nonparental-type)offspring

RESULTS



Morgan and Linked Genes: Same Chromosome

Body ColorGrey Blackb+ b

Wing TypeLong Shortvg+ vg

bvg

b+vg+ bvg

b+bvg+vg bbvgvg

From Mendel if linked –no recombinant gametesBUT NOT THE CASE?

50:50

Figure 15.5




normal wings)


b+ b+ vg+ vg+

x

b b vg vg


b+ b vg+ vg

b b vg vg

TESTCROSS

x


b vg


965Wild type

(gray-normal)

944Black-

vestigial

206Gray-

vestigial

185Black-normal

Sperm



RESULTS






Figure 15.5




normal wings)


b+ b+ vg+ vg+

x

b b vg vg


b+ b vg+ vg

b b vg vg

TESTCROSS

x


b vg


965Wild type

(gray-normal)

944Black-

vestigial

206Gray-

vestigial

185Black-normal

Sperm



RESULTS







bvg

b+vg+ bvg

b+bvg+vg bbvgvg

From Mendel if linked –no recombinant gametesBUT NOT THE CASE?

50:50

Meiosis increases DIVERSITY

(2) Recombination “cross over” between homologous chromosomes.

A A

B B

a a

b b

A A

B B

a a

b b

M P

Sister chromatids

Synapsis (DNA exchange)

Tetrad Chiasma(physical site of cross over)

Recombination

A A

B b

A A

B b B

a a

b B

a a

b

4 different Gametes


Meiosis increases DIVERSITY

(2) Recombination “cross over” between homologous chromosomes.

A AB B

a ab b

M P

Sister chromatids

Synapsis (DNA exchange)

Tetrad Chiasma(physical site of cross over)

Recombination

A

A

B b

A

AB

B b

a

a

b B

a a

b

4 different Gametes

A AB b

a aB b


Human Genetics - Pedigrees

•Alleles segregate independently in meiosis

•Dominate and recessive alleles exist

•Family Tree or Pedigrees used in analysis

= female

= maleNo phenotype

= female

= maleCarriers (heterozygous)

= marriage

= marriage between blood relatives

Helps us analzye recessive, dominant, and sex linked,

inherited disorders

= female

= maleHave disease


One of the parentsIs carrier

Ex. Sickle cellCystic fibrosis

Husband has to be carrier

All daughter are carriers

Human Genetics - Pedigrees

Ex. Achondroplasia(Dwarfism) Ex. Retinitis Pigmentosa

(progressive blindness)


Mitochondrial DiseasesHow it is inherited?

•Mitochondria has its own DNA

•Mutations that arise in mitochondrial DNA can be inherited – HOW?

•From the maternal gamete•Mitochondria are only donated from maternal gamete!!!

•Mothers only pass disease to children (not from fathers)!!!


Diseases due to Chromosomal abnormalities!

•Non-disjunction

•2 homologs don’t separate in meiosis I

•Sister chromatids don’t separate in meiosis II

•Creates Aneuploid gametes: incorrect number of gametes

n + 1 = 1 extran – 1 = 1 missing

Zygote 2n + 1 Trisomy (Down Syndrome)

- 1 monosomy

Too much or too little proteins made from that chromosome

Ploidy = # copies of genome in an organism


genetics part i mendel - university of california, san...

Documents