MENDELIAN INHERITANCE: Monohybrid cross

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Monohybrid inheritance:

Complete dominanceMonohybrid crossPhenotypeGenotypeDominantrecessiveModification of the 3:1 ratioIncomplete dominanceCodominance

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Radishes may have any of the three shapes: long, spherical and ovoid. Crosses of long x spherical always produce an F1 consisting of only ovoid radishes.What is the genotype of a long, spherical and ovoid traits? (use the first letter of your name to designate genotype)How does the pair of gene behaves in terms of dominance or recessiveness?

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Lethal genes

A lethal gene is one that causes the death of an organism.Pedigree shows the pattern of inheritance for a characteristic within a group of people.

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Medicine is concerned with the disorders of human beings and may of these are inherited as dominant or recessive phenotypes in simple mendelian mannerPropositus or index case individual who comes to the attention of a physician as patient. If there is a family history of the disorder, a pedigree is constructed as far as available information allows; then analyzed

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AUTOSOMAL DOMINANT INHERITANCE

The pattern of autosomal dominant inheritance is perhaps the easiest type of Mendelian inheritance to recognize in a pedigree. One dose of the mutant gene, one mutant allele, is all that is required for the expression of the phenotype. There are three reasons why an individual with an autosomal dominant disease should always be considered as being a heterozygote until proven otherwise:

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The disease is usually rare, with only about 1/10,000 individuals affected as an order of magnitude.

To produce a homozygote, two affected heterozygotes would have to mate. This probability is 1/1,000,000 and then they would have only a 1/4 chance of having a homozygous affected offspring.

Affected individuals are most likely to come from affected by normal matings.

The normal parent is homozygous recessive, thus assuring that each product of the mating has at least one normal gene.

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In the extremely rare instances where two affected individuals have mated, the homozygous affected individuals usually are so severely affected they are not compatible with life. The exceptions are the autosomal dominant diseases caused by the somatic expansion of trinucleotide repeat sequences (e.g., Huntington's disease) that we will study later.

The mating of very closely related individuals, the most likely way for two affected individuals to know each other, is forbidden in our society.

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Autosomal dominant disorder

A child who has a condition must have a parent with the condition unless a mutationUsually an offspring with a dominant genetic disorder has one heterozygous parents and one homorecessive parentTherefore 50% chance of getting the faulty gene,

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Dominant

Achondroplasia (dwarfism): AA = Homozygous dominant is lethal - fatal (spontaneous abortion of fetus). Aa = dwarfism. aa = no dwarfism. 99.96% of all people in the world are homozygous recessive (aa)..Polydactyly (extra fingers or toes): PP or Pp = extra digits, pp = 5 digits. 98% of all people in the world are homozygous recessive (pp).

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Progeria (very premature aging): Spontaneous mutation of one gene creates a dominant mutation that rapidly accelerates aging

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Huntingtons dse.

Characterized by involuntary jerking of the body and a progressive degeneration of the nervous system, accompanied by gradual mental and physical deterioration.The mean age of onset of these symptoms is between 35-40.Chromosome 4

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The family represented by Pedigree 1 is a good example of how autosomal dominant diseases appear in a pedigree.

Each of the four hallmarks of autosomal dominant inheritance are fulfilled.

Each affected individual has an affected parent; there is no skipping of generations.

Males and females are equally likely to be affected. About 1/2 of the offspring of an affected individual are affected (the recurrence risk is 1/2).

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Normal siblings (II-3) of affected individuals have all normal offspring.

Low density lipoprotein receptors are structural proteins or polypeptides, not enzymes.

If III-1, an affected female, were to produce a child that child would have a 1/2 chance of being normal and a 1/2 chance of being affected.

If her normal brother, III-2, were to produce a child that child would have a nearly 0 chance of being affected.

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AUTOSOMAL RECESSIVE INHERITANCE

A genetic disorder is recessive when an affected child ids born to parents who appear normal.Parents with heterozygous- carry a faulty gene- carriers.Example; albinism absence of pigment in the skin, hair and iris of the eye.

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There are five hallmarks of autosomal recessive inheritance:

1. Males and females are equally likely to be affected.

2. On average, the recurrence risk to the unborn sibling of an affected individual is 1/4.

3. The trait is characteristically found in siblings, not parents of affected or the offspring of affected.

4. Parents of affected children may be related. The rarer the trait in the general population, the more likely a consanguineous mating is involved.

5. The trait may appear as an isolated (sporadic) event in small sibships.

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The above pedigree illustrates four of the five hallmarks of autosomal recessive inheritance. I-1 and I-2 are unrelated, yet they produced an affected offspring (affected offspring have normal parents). By chance, they both must have been carriers. Even though II-2 is affected, she produced no affected offspring (trait appears in siblings, not parents or offspring).

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By far the most probable genotype for an individual from outside the family (II-1) is homozygous normal. III-1, III-2 and III-3 are all obligate carriers (heterozygotes), since they are not affected but could only have inherited the recessive gene from II-2 II-3, II-5, and II-6 each have a 2/3 chance of being a carrier and a 1/3 chance of being homozygous normal. They are not affected, but they come from a carrier x carrier mating. II-4 and II-7 have a high probability of being homozygous normal since they are from outside the family. III-4, III-5, III-6, III-7, III-8, and III-9 all have a 1/3 chance of being carriers and a 2/3 chance of being homozygous normal. One parent of each is probably homozygous normal, the other has a 2/3 chance of being a carrier and a 1 in 2 chance of passing on the recessive allele if they were a carrier.

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In rare autosomal recessive diseases, when consanguinity is involved, those individuals in the direct line of descent within the family are considered to be carriers and those individuals from outside the family are considered homozygous normal unless there is evidence to the contrary.

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Sickle-cell disease: The most common inherited disease of African-Americans (1:400 affected). Homozygous recessives (ss) make abnormal form of hemoglobin that deforms red blood cells and causes a cascade of symptoms (clogging of blood vessels, organ damage, kidney failure).

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Cystic fibrosis

Homozygous recessives (cc) have cystic fibrosis - body cannot make needed chloride channel, high concentrations of extracellular chloride causes mucous to build up, infections, pneumonia. Diet, antibiotics and treatment can extend life to 25 years or more.Chromosome 7

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Tay-Sachs: Enzyme that breaks down brain lipids is non-functional in homozygous recessives (tt). Buildup of lipids causes death by age 2-3

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Problem solving:

A normal woman marries a man with sickle trait. What is the probability of their having a A child with sickle cell trait?A normal child?A child with sickle cell anemia?

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Phenylketonuria (PKU) is a heritable condition in humans characterized by inability to metabolize the amino acid and phenylalanine because of failure to produce the enzyme phenyl alanine hydroxylase. Among other symptoms PKU develop a severe mental retardation. PKU are born to parents who are not PKUsIs the gene responsible for phenylketonuria completely dominant or recessive?In as much as PKU rarely reproduce, why does such a disadvantageous gene persist in the population?

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Silky feathers in fowl is recessive to of normal feathers.If 60 birds were raised from a cross between individuals that were heterozygous for this gene, how many would be expected to be silky and how many normal?If you had a normal feathered bird, what would be the easiest way to determine whether it is homozygous or heterozygous.

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Dentinogenesis imperfecta (opalescent dentine) is an hereditary tooth disorder characterized by defective dentine that splits from stress due to normal biting and chewing and ocuurs in about 1:8,000 persons. Teeth of affected persons range in color from amber to opalescent blue. Affected children occur only in families where one or both parents have opalescent dentine: children with normal dentine may have parents who are both normal, or one normal and one affected or both affected.Is the gene condition completely dominant, codominant, incompletely dominant or recessive?

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