Human Genetics & Inheritance Patterns

• In the space below list a number of differences and similarities found among humans.

Differences:

Similarities:

• You may be able to list more similarities than differences.

• Many (but not all) of the features we listed are genetic mutations.

Note to me…

• Do the taster/non-taster lab!

Mutations

• We have learned that DNA is responsible for the production of proteins that direct an organism’s metabolism and development.

• What would happen if there were changes in our DNA?

• On a rare occasion it may result in NEW PHENOTYPES.

• A change in DNA is called a MUTATION • These changes can affect an entire chromosome or specific

genes. Any cells in our bodies are subject to mutations. – Mutations in our SEX CELLS (egg or sperm) are called GERM CELL

MUTATIONS.

• These mutations do not affect the organism but are passed to offspring.

• Most of the mutations that occur in germ cells are lethal and do not allow the individual to develop past the zygote stage.

• Mutations that occurs in other body cells are called SOMATIC MUTATIONS . These mutations are passed to daughter cells through mitosis.

• These mutations do not affect the offspring of the affected individual.

CHROMOSOMAL MUTATIONS:• During cell division mutations may occur in

chromosomes. There are four types of chromosomal mutations:1. DELETION

• 2. INVERSION

• 3. TRANSLOCATION

• 4. NONDISJUNCTION

__Deletion_ :

• When a piece of the chromosome breaks off. This results in the information on that chromosome piece being lost.

__INVERSION____ :

• When a piece breaks off from a chromosome and reattaches itself to the chromosome in reverse order.

_TRANSLOCATION:

• When a broken piece attaches to a non-homologous chromosome.

Nondisjunction

• A fourth type of chromosomal mutation is called NONDISJUNCTION .

• This occurs when a replicated chromosome pair fails to separate during cell division.

• The daughter cells will result in one having an extra copy of a chromosome and the other cell lacking that chromosome entirely.

GENE MUTATION:• Scientist have found several mutations

that can occur in the DNA sequence.

• If the mutation only affects one nitrogen base is called a POINT MUTATION.

• If one nitrogen base is replaced by another

nitrogen base the DNA may code for different AMINO ACID . – If one nitrogen base is added or deleted a

FRAME SHIFT MUTATION occurs. This usually results in the inability of the DNA to code for the correct amino acid.

Some mutations happen by CHANCE. There are other times when mutations are caused by MUTAGENS, environmental factors that result in that damage of DNA strands.

MUTAGENS:

• A few well known mutation causing factors are :

– cigarette tars, – asbestos, and – viruses. – Radiation is also an environmental factor that

causes mutations in both germ and somatic cells.

Spontaneous vs Induced Mutations:• All mutations are described as either

spontaneous or induced.

• We have already discussed the mutations that are induced.

• Spontaneous mutations are considered as those that arise in nature. No specific agent other than natural forces is associated with their occurrence.

• These mutations are assumed to arise randomly as in changes in the nucleotides sequence of genes.

• All mutations have a cause , but some mutations occur in the absence of mutagens, or mutation-causing agents.

Some of these mutations are the result of miscues of the DNA REPLICATION MACHINERY. Sometimes the proofreading mechanism fails and the mistake is not caught.

SPONTANEOUS MUTATIONS • These type of mutations can occur in several

ways: – (1) As DNA is replicating, mistakes are made on

occasion that go uncorrected. – (2) The bases in the DNA template strand or in the

newly inserted nucleotide can shift to an alternate form that base-pairs incorrectly.

– (3) Too many or too few bases can be inserted , causing frame-shift mutations.

CHEMICAL MUTAGENESISInduced Mutatuions• Different chemicals induce different kinds

of DNA damage.

• Nitrous acid and bisulfite cause deamination – (the removal of an amino group [NH2] that

converts cytosine to uracil) of bases.

RADIATION- INDUCED MUTATIONS

• Ultraviolet, gamma, and X-radiation are the common types of mutagenic radiation.

• Ultraviolet radiation is relatively week so the damage it causes is relatively modest: it cross-links adjacent pyrimidines on the same DNA strand, – Forming a dimer, usually a

THYMINE DIMER.

What’s a dimer? (FYI only, not in notes)

• A dimer is a chemical or biological entity consisting of two subunits called monomers, which are held together by either intramolecular forces (covalent bonds) or weaker intermolecular forces.

• Molecular dimers are often formed by the reaction of two identical compounds

• An example of an intermolecular or physical dimer is acetic acid wherein hydrogen bonds hold the two molecules together. The water dimer is another such dimer.

• This blocks DNA replication because the replication machinery cannot tell which bases to insert opposite the dimers.

– Other times an alternate form of a nitrogen base is used that bonds with the alternate form of nitrogen bases.

– Example there are two forms of Thymine one will bond with the usual Adenine and the other form will bond with Guanine:

• Replication sometimes proceeds anyway and bases are inserted at random .

• If these are the wrong bases, a mutation results.

Radiation:

• The kind of radiation that is most damaging to DNA has a wavelength of about 260 nm, – which is not surprising since this is the wavelength

of radiation that is most absorbed most strongly by DNA.

– This type of radiation is also abundant in sunlight, so most forms of life are exposed to this type of radiation to some extent.

– This type of mutation explains why sunlight can cause skin cancer.

– We have a shield from this type of radiation. – The natural shield is the OZONE layer in the earth’s

upper atmosphere. This ozone absorbs the bulk of such radiation.

Gamma and X rays. • Gamma and X rays have

more energy that ultraviolet radiation. These types of radiation can interact directly with DNA molecule. These types of radiation can cause the DNA to break apart.

Effects on Organism

• Scientist also classify mutations on the basis of their effect on the organism: – 1. Morphological

trait mutations: • These mutations

affect the morphology or shape of the organism:

– 2. Biochemical mutations: These mutations affect how an organism accomplishes nutrition. One example is the inability of an organism to synthesize an amino acid.

• Also these types of mutations may affect an organisms chemical processes such as gas exchange: i.e. sickle cell anemia.

• 3. Lethal mutations: these mutations will cause the death of the organism. – One example of a lethal mutation is

Tay-Sachs or Huntingtons disease.

• Sometimes the lethal mutations will cause immediate death

• or as in the above mentioned disease death may come at a later time in the life of the human.

Morphological Mutations: • Complex multicellular organisms carrying

• MORPHOLOGICAL MUTATIONS (visible mutations), can usually be distinguished from wild-type (most common variant of a gene).

– –One example , albino mammals have a mutation in a gene that is responsible for dark coat (or skin) pigment.

–The mutation is usually in the gene that codes for TYROSINASE, the key enzyme that leads to the production of MELANIN the black pigment in hair, eyes, and skin.

• A mutated tyrosinase gene may produce no active enzyme, so no melanin can be made.

• As a result humans have very fair skin and light blue eyes, albino mice have white fur and pink eyes.

LETHAL MUTATIONS:

• Some mutations are so severe that an organism carrying them cannot survive at all.

• These types of mutations are called LETHAL mutations.

• When a genetic defect causes 100% mortality it is termed lethal allele.

Lethals Cont.

• Lethals are generally recessive resulting in the death of the zygote that is homozygous recessive.

• n 1904 French geneticist Lucien Cue’not carried out crosses on coat color in mice.

• He obtained results that were not consistent with Mendelian predictions.

• He observed that yellow body color alleles were dominant. When he crossed two heterozygous yellow mice he observed 2:1 ratio of yellow to wild type (brown- agouti). What ratio did he expect:

• 3:1 Wild to yellow

• He learned that all the Homozygous yellow mice died in utero.

• Histological observations validated this conclusion which demonstrated 1/4 of the embryos from yellow x yellow crosses failed to develop.

• This demonstrates that lethal mutations in diploid organisms are recessive .

• If one parent contributes a defective gene for an essential protein and the other contributes a wild-type gene, the latter will usually allow the cell to make enough protein to compensate.

• It is only when two defective genes come together in a individual that lethality results.

Conditional Mutations: • There are certain mutations that can be lethal

under certain conditions.

• These mutations are called CONDITIONAL LETHALS.

• Temperature Sensitive: – There are certain mutations called TEMPERATURE-

SENSITIVE (or “ts”) mutations.

• This mutation allows for growth at low temperatures but not at normal growth temperatures.

• Lethality in this case is conditional on temperature.

• It is important to realize that it is the PROTEIN PRODUCT that is temperature sensitive, NOT THE GENE ITSELF.

• This type of mutation creates an altered protein that is easily DENATURED. (EGG WHITE).

• This type of mutations can be observed in humans. – CYSTIC FIBROSIS is caused by a mutant gene

whose protein product cannot fold properly at normal body temperature, so it remains inactive.

– At lower temperatures it functions normally.

• Genetic mutations can be conditional without being lethal.

• One example is Siamese cats. – These animals have a mutation

in the gene for DARK coat color.

• Siamese cats have dark patches on their feet , faces and ears can you explain this mutation.

Conditional without lethality

• Patches on their feet, faces , and ears are normal where the temperature is somewhat lower than the rest of the body

• where the protein has been denatured.(lighter in color)

MISSENSE and NONSENSE MUTATIONS• Many point mutations are MISSENSE

MUTATIONS, in which a base change alters the sense of a codon from one amino acid to another. – This causes an improper amino acid to be

inserted into the protein product of the mutated gene. for example a missense mutation might change the proline codon CCG to ARGININE codon CGG. .

• An example of such a defect is SICKLE-CELL DISEASE, a true genetic disease.

• People who are homozygous normal for this condition have normal looking red blood cells when their blood is rich in oxygen.

• The shape of normal cells is disc shape that is concave.

• When people with this disorder exercise there is a depletion of oxygen in their blood this creates a change in the morphology of their red blood cells.

• The sickling is caused when mutated hemoglobin precipitates under low oxygen conditions.

• The red blood cells forms a crescent (sickle) shape.

• The sickle cells cannot fit through tiny capillaries so they clog and rupture the capillaries.

• This causes internal bleeding and pain. The sickle blood cells also burst and leave the patient ANEMIC.