Download - 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
Alleles of a given gene are not identical
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
Mendelian GeneticsThe laws of heridity
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.
Mendelian GeneticsThe laws of heridity
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
Linked Genes
• Genes found on same chromosome will be inherited together
• do not exhibit independent assortment
Mendelian GeneticsThe laws of heridity
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!!
Mendelian GeneticsThe laws of heridity
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
Mendelian GeneticsThe laws of heridity
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
Modes of HeredityAutosomal Dominant
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
Modes of HeredityAutosomal Dominant
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