Genetics and inheritance

Genetics and inheritance

In your own words, explain the following terms

1. Chromosome2. Gene3. Features4. Gametes5. Zygote6. Diploid7. Allele8. Homozygous9. Heterozygous10. Selective breeding11. Genetic engineering12. Meiosis13. Mitosis14. Sexual reproduction15. Asexual reproduction16. Mutations17. Dominant 18. Recessive

The instructions that tell cells what we look like are carried in these. There are 23 pairs of them in a normal human cell.

These are the units which make up chromosomes. Responsible for inheritance of specific characteristics

Cellular Functions of Human Genes

These are things like eye colour, skin colour and hair colour.

They are controlled by genes.

Sperm and egg cells are both this type of cell.Contain half the amount of DNA of normal diploid cells

When a sperm and egg cell fuse together,

they produce this.

We use this word to describe cells which contain the full

complement of genetic material. In humans this would be

46 chromosomes (23 pairs)

The different versions of genes One of two to many alternative forms of the same gene (eg., round allele vs. wrinkled allele; yellow vs. green). Alleles have different DNA sequences that

cause the different appearances we see.

Alleles of a given

gene are identical

(can be either

dominant or recessive

http://www.blc.arizona.edu/courses/181gh/rick/genetics2/graphics/fly1.gif

Alleles of a given gene are not identical

http://www.blc.arizona.edu/courses/181gh/rick/genetics2/graphics/fly1.gif

Where plants and animals with useful or desired traits are bred together

to produce offspring with those desired traits

The altering of the character of an organism by

inserting genes from another organism

Division of a cell to produce 2 daughter cells which each has the same

number and kind of chromosomes as the mother cell

Type of reproduction that involves fusion of gametes

Reproduction whereby

individuals are produced from a single

parent

asexual

repro

duction

Random change in the genetic material of the cell

The allele that is expressed where an individual is heterozygous

The allele that is ‘hidden’ (not expressed) when an individual is heterozygous

for a given gene

Mendelian GeneticsThe laws of heridity

Gregor Mendel (1822-1884): “Father of Genetics”

Augustinian Monk at Brno Monastery in Austria (now Czech Republic)-> well trained in math, statistics, probability, physics, and interested in plants and heredity.Mountains with short, cool growing season meant pea (Pisum sativum) was an ideal crop plant.

• Work lost in journals for 50 years!

• Rediscovered in 1900s independently by 3 scientists

• Recognized as landmark work!

Garden Pea

• Pisum sativum• Diploid• Differed in seed shape, seed color,

flower color, pod shape, plant height, etc.

• Each phenotype Mendel studied was controlled by a single gene.

Terms

• Wild-type is the phenotype that would normally be expected.

• Mutant is the phenotype that deviates from the norm, is unexpected but heritable.

• This definition does not imply that all mutants are bad; in fact, many beneficial mutations have been selected by plant breeders.

Advantages of plants

• Can make controlled hybrids.• Less costly and time consuming to

maintain than animals.• Can store their seed for long periods

of time.• One plant can produce tens to

hundreds of progeny.

Advantages of plants

• Can make inbreds in many plant species without severe effects that are typically seen in animals.

• Generation time is often much less than for animals.– Fast plants (Brassica sp.)– Arabidopsis


1. The Law of Segregation: Genes exist in pairs and alleles segregate from each

other during gamete formation, into equal numbers of gametes. Progeny obtain one determinant from each parent.

-> Alternative versions of genes account for variations in inherited characteristics (alleles)

-> For each characteristic, an organism inherits two alleles, one from each parent. (-> homozygote/heterozygote)

-> If the two alleles differ, then one, the allele that encodes the dominant trait, is fully expressed in the organism's appearance; the other, the allele encoding the recessive trait, has no noticeable effect on the organism's appearance (dominant trait -> phenotype)

-> The two alleles for each characteristic segregate during gamete production.

The Principle of Segregation

• Genes come in pairs and each cell has

two copies.

• Each pair of genes can be identical

(homozygous) or different (heterozygous).

• Each reproductive cell (gamete) contains

only one copy of the gene.

Mendel’s Principle of Segregation

• In the formation of gametes, the paired

hereditary determinants separate (segregate)

in such a way that each gamete is equally

likely to contain either member of the pair.

• One male and one female gamete combine to

generate a new individual with two copies of

the gene.

Principle of Segregation(Mendel’s First Law)

Parental Lines

Round Wrinkled

X

All round F1 progeny

Self-pollinate

Round5474

Wrinkled1850

3 Round : 1 Wrinkled

Important Observations

• F1 progeny are heterozygous but express only one phenotype, the dominant one.

• In the F2 generation plants with both phenotypes are observedsome plants have recovered the recessive phenotype.

• In the F2 generation there are approximately three times as many of one phenotype as the other.

Mendel’s Results

Parent CrossParent Cross FF11 Phenotype Phenotype FF22 data data

Round x Round x wrinkledwrinkled

RoundRound 5474 : 5474 : 18501850

Yellow x greenYellow x green YellowYellow 6022 : 6022 : 20012001

Purple x whitePurple x white PurplePurple 705 : 224705 : 224

Inflated x Inflated x constricted podconstricted pod

InflatedInflated 882 : 299882 : 299

Green x yellow Green x yellow podpod

GreenGreen 428 : 152428 : 152

Axial x terminal Axial x terminal flowerflower

AxialAxial 651 : 207651 : 207

Long x short Long x short stemstem

LongLong 787 : 277787 : 277

3 : 1 Ratio

• The 3 : 1 ratio is the key to interpreting Mendel’s data and the foundation for the the principle of segregation.

Round vs. Wrinkled

Parental Lines

Round Wrinkled

X

All round F1 progeny

Self-pollinate

Round5474

Wrinkled1850

3 Round : 1 Wrinkled

A Molecular View

Parents F1 F2 Progeny

WW ww Ww ¼WW ¼Ww ¼wW ¼ww

1: 2 : 1 Genotype = 3: 1 Phenotype

One Example of Mendel’s Work

TallP

Dwarfx

F1All Tall

Phenotype

Clearly Tall is Inherited…What happened to Dwarf?

F1 x F1 = F2

F23/4 Tall1/4 Dwarf -> Phenotype: 3:1

Dwarf is not missing…just masked as “recessive” in a diploid state

1. Tall is dominant to Dwarf

2. Use D/d rather than T/t for symbolic logic

DD dd

Dd

Genotype

HomozygousDominant

HomozygousRecessive

Heterozygous

DwarfDwarfdddd

TallTallDdDddd

TallTallDdDd

TallTallDDDDDD

ddDDPunnett Square:

possible gametes

possible gametes

Dihybrid crosses reveal Mendel’s law of independent

assortment• A dihybrid is an individual that is

heterozygous at two genes

• Mendel designed experiments to determine if two genes segregate independently of one another in dihybrids

• First constructed true-breeding lines for both traits, crossed them to produce dihybrid offspring, and examined the F2 for parental or recombinant types (new combinations not present in the parents).

Mendel and two genes

xRoundYellow

WrinkledGreen

All F1 Round, Yellow

RoundYellow

315

RoundGreen108

WrinkledYellow

101

WrinkledGreen

32

Dihybrid cross produces a predictable ratio of phenotypes

genotype phenotype number phenotypic ratio

• Parent Y_R_ 315 9/16

• Recombinant yyR_ 108 3/16

• Recombinant Y_rr 101 3/16

• Parent yyrr 32 1/16

Ratio of yellow (dominant) to green (recessive)=3:1 (12:4)

Ratio of round (dominant) to wrinkled (recessive)=3:1 (12:4)

Ratio for a cross with 2 genes

• Crosses with two genes are called dihybrid.

• Dihybrid crosses have genetic ratios of 9:3:3:1.

Mendel and two genes

RoundYellow

315

RoundGreen108

WrinkledYellow

101

WrinkledGreen

32

Round = 423Wrinkled = 133

Yellow = 416Green = 140

Each gene has a 3 : 1 ratio.Each gene has a 3 : 1 ratio.

Summary of Mendel's work

• Inheritance is particulate - not blending

• There are two copies of each trait in a germ cell

• Gametes contain one copy of the trait

• Alleles (different forms of the trait) segregate

randomly

• Alleles are dominant or recessive - thus the

difference between genotype and phenotype

• Different traits assort independently

Rules of Probability

Independent events - probability of two events occurring together

What is the probability that both A and B will occur?Solution = determine probability of each and multiply

them together.

Mutually exclusive events - probability of one or another eventoccurring.

What is the probability of A or B occurring?Solution = determine the probability of each and add

them together.


2. The Law of Independent AssortmentMembers of one pair of genes (alleles) segregate independently of members of other pairs.

-> The emergence of one trait will not affect the emergence of another.

-> mixing one trait always resulted in a 3:1 ratio between dominant and recessive phenotypes-> mixing two traits (dihybrid cross) showed 9:3:3:1 ratios-> only true for genes that are not linked to each other

3:1

9:3:3:1

http://en.wikipedia.org/wiki/Genetic_linkage

Linked Genes

• Genes found on same chromosome will be inherited together

• do not exhibit independent assortment


Problems with doing human genetics:

-> Can’t make controlled crosses!

-> Long generation time

-> Small number of offspring per cross

So, human genetics uses different methods!!


Major method used in human genetics is -> pedigree analysis(method for determining the pattern of inheritance of any trait)

Pedigrees give information on:

-> Dominance or recessiveness of alleles

-> Risks (probabilities) of having affected offspring


Standard symbols used in pedigrees:

carrier

”inbreeding”

Modes of HeredityAutosomal Dominant

Most dominant traits of clinical significance are rare

So, most matings that produce affected individuals are of the form:

Aa x aa

-> Affected person can be heterozygote (Aa) or homozygote (AA)-> Every affected person must have at least 1 affected parent-> expected that 50% are affected /50% are uneffected-> No skipping of generations-> Both males and females are affected and capable of transmitting the trait-> No alternation of sexes: we see father to son, father to daughter, mother to son, and mother to daughter

Autosomal dominant disorders

• both homozygotes and heterozygotes are affected

• usually heterozygotes (inherited from one parent)

• both males and females are affected• transmission from one generation to

the other• 50% of children are affected


Examples:

Tuberous sclerosis (tumor-like growth in multiple organs, clinical manifestations include epilepsy, learning difficulties, behavioral problems, and skin lesions)

and many other cancer causing mutations such as retinoblastoma

Brachydactyly


Examples: Achondroplasia

-> short limbs, a normal-sized head and body, normal intelligence

-> Caused by mutation (Gly380Arg

mutation in transmembrane domain) in the FGFR3 gene

-> Fibroblast growth factor receptor 3 (Inhibits endochondral bone growth by inhibiting chondrocyte proliferation and differentiation

Mutation causes the receptor to signal even in absence of ligand -> inhibiting bone growth

-> Affected person must be homozygote (aa) for disease allele-> Both parents are normal, but may see multiple affected individuals in the sibship, even though the disease is very rare in the population-> Usually see “skipped” generations. Because most matings are with homozygous normal individuals and no offspring are affected-> inbreeding increases probablility that offspring are affected-> unlikely that affected homozygotes will live to reproduce

These are likely to be more deleterious than dominant disorders, and so are usually very rare

The usual mating is:

Aa x Aa

Autosomal RecessiveModes of Heredity

Autosomal recessive

• majority of mendelian disorders• only homozygotes are affected,

heterozygotes (parents) are only carriers• 25% of descendants are affected• if the mutant gene occurs with low

frequency - high probability in consanguineous marriages

• onset of symptoms often in childhood• frequently enzymatic defect• testing of parents and amnial cells

Autosomal RecessiveModes of Heredity

Examples:

Sickle-Cell Anaemia (sickling occurs because of a mutation in the hemoglobin gene -> affects O2 transport; occurs more commonly in people (or their descendants) from parts of tropical and sub-tropical regions where malaria is common -> people with only one of the two alleles of the sickle-cell disease are more resistant to malaria)

Cystic fibrosis (also known as CF, mucovoidosis, or mucoviscidosis; disease of the secretory glands, including the glands that make mucus and sweat; excess mucus production -> causing multiple chest infections and coughing/shortness of breath; especially Pseudomonas infections are difficult to treat -> resistance to antibiotica)

Dominant vs. RecessiveModes of Heredity

Is it a dominant pedigree or a recessive pedigree?

1. If two affected people have an unaffected child, it must be a dominant pedigree: A is the dominant mutant allele and a is the recessive wild type allele. Both parents are Aa and the normal child is aa.

2. If two unaffected people have an affected child, it is a recessive pedigree: A is the dominant wild type allele and a is the recessive mutant allele. Both parents are Aa and the affected child is aa.

3. If every affected person has an affected parent it is a dominant pedigree.

-> Act as recessive traits in females (XX) -> females express it only if they get a copy from both parents) -> dominant traits in males (XY)-> An affected male cannot pass the trait on to his sons, but passes the allele on to all his daughters, who are unaffected carriers-> A carrier female passes the trait on to 50% of her sons

Examples: About 70 pathological traits known in humans -> Hemophilia A, Duchenne muscular dystrophy, color blindness,…..

X-Linked RecessiveModes of Heredity

X-linked diseases

• transmitted by heterozygous mother to sons• daughters - 50% carriers, 50% healthy• sons - 50% diseased, 50% healthy• Children of diseased father - sons are

healthy, all daughters are carriers• Hemophilia A• Hemophilia B • Muscle dystrophy• ->Most of mental retardation

X-linked dominant:

-> caused by mutations in genes on the X chromosome-> very rare cases-> Males and females are both affected in these disorders, with males typically being more severely affected than females. -> Some X-linked dominant conditions such as Rett syndrome, Incontinentia Pigmenti type 2 and Aicardi Syndrome are usually fatal in males

Y-linked (dominant):

-> mutations on the Y chromosome. -> very rare cases -> Y chromosme is small-> Because males inherit a Y chromosome from their fathers -> every son of an affected father will be affected. -> Because females inherit an X chromosome from their fathers -> female offspring of affected fathers are never affected.-> diseases often include symptoms like infertility

Other sex-linked diseaseModes of Heredity

Mitochondrial inheridance:

Mitochondrial DNA is inherited only through the egg, sperm mitochondria never contribute to the zygote population of mitochondria. There are relatively few human genetic diseases caused by mitochondrial mutations.

-> All the children of an affected female but none of the children of an affected male will inherit the disease.-> Note that only 1 allele is present in each individual, so dominance is not an issue

Exceptions to Mendelian Inheritance

Modes of Heredity

Summary of mutations which can cause a disease

• Three principal types of mutation– Single-base changes– Deletions/Insertions– Unstable repeat units

• Two main effects– Loss of function– Gain of function

Pedigree

• Use Mendelian principles to assemble information on family traits

• Study inheritance patterns when can’t perform test cross

• Genetic counseling• Track genetic disorders

• Carriers– Carry allele for recessive disorder- do not

exhibit symptoms

Albinism PedigreeCarrier

Single gene disorders

• One gene controls the disorder

• Exhibit simple inheritance patterns

• Can be dominant or recessive

Recessive Disorder

• Homozygous recessive• Bulk of human genetic disorders • Vary in effect

– Albinism– Tay Sachs

• Inbreeding– Mating of close relatives– Increases frequency of homozygous

recessive genotypes??

Albinism

Inbreeding

Polydactyly

Dominant Disorders

• Disease expressed with only 1 allele present

• Maintained in population because– Not lethal

• Achondroplasia• Webbing• Extra digits

– Develop post- reproductive age• Huntington disease

Dominant disordersSyndactyly

Dominant disorders Polydactyly

Achondroplasia

Other Patterns of Inheritance

• Incomplete dominance

• Codominance

• Pleiotrophy

• Polygenic inheritance

Incomplete dominance

• Pattern of inheritance in which the heterozygous (Aa) phenotype is intermediate between the phenotypes of the homozygous parents (AA & aa)

Incomplete Dominance

Sickle Cell ANemia

codominance

• The expression of two different alleles of a gene in a heterozygous condition

• Example AB0 blood group

Co dominance

Pleiotropy

• The control of more than one phenotypic characteristic by a single gene

• One gene many effects

Polygenic inheritance

• The additive effect of two or more gene loci on a single phenotypic characteristic

• Majority of characteristics

• Example skin color

Polygenic inheritance

Sex-chromosomes

Sex linked genes

• Gene located on a sex chromosome• X chromosome contains more genes than Y

chromosome• Sex linked inheritance

– Males pass y linked only to sons– Males pass x linked only to daughters– Females can pass x linked to either sons or daughters

Sex linked disorders

• Recessive sex linked• Y linked recessive always exhibited in males• X linked recessive exhibited in males and

homozygous females• X linked dominant traits exhibited in both Males

& female carriers• Color blindness (X)• Hemophilia

– X linked recessive

Hemophilia

Y Linked disorders

• Androgen Insensitivity disorder– XY genetics yield female phenotype as a result of an

inability to respond to testosterone– Error in membrane protein receptors

• Congenital adrenal hyperplasia– Xx genotype yield female with male genitalia– Masculinization of genitals & defects in adrenal gland

function

• Deletion– Loss

• Duplication– Added chromosome

Translocation

Fragile X Syndrome

Duplication

Documents

Genetics and inheritance