1. Human Genetics

2. Mutations A change in the genes amount or a new allele of a gene.
Brings change into a species
Most are harmful
Some have no effect
Few are beneficial

3. Types of mutation Alterations in chromosome structure
Sometimes, chromosomes break, leading to 4 types of changes in chromosome structure:

4. Deletion
A portion of one chromosome is lost during cell division. That chromosome is now missing certain genes. When this chromosome is passed on to offspring the result is usually lethal due to missing genes.

5. Example - Cri du chat (cry of the cat): A specific deletion of a small portion of chromosome 5; these children have severe mental retardation, a small head with unusual facial features, and a cry that sounds like a distressed cat.

6. Duplication
If the fragment joins the homologous chromosome, then that region is repeated

7. Example - Fragile X: the most common form of mental retardation
Example - Fragile X: the most common form of mental retardation. The X chromosome of some people is unusually fragile at one tip - seen "hanging by a thread" under a microscope. Most people have 29 "repeats" at this end of their X-chromosome, those with Fragile X have over 700 repeats due to duplications. Affects 1:1500 males, 1:2500 females.

8. Inversion
A fragment can be broken and rejoined in the reverse orientation, reversing the fragment within a chromosome

9. Translocation
A fragment is moved from one chromosome to another - joins a non-homologous chromosome. The balance of genes is still normal (nothing has been gained or lost) but can alter phenotype as it places genes in a new environment.

10. Alterations in chromosome number
Nondisjunction occurs when either homologous chromosomes fail to separate during anaphase I of meiosis, or sister chromatids fail to separate during anaphase II. The result is that one gamete has 2 copies of one chromosome and the other has no copy of that chromosome. (The other chromosomes are distributed normally.)
If either of these gametes unites with another during fertilization, the result is aneuploidy (abnormal chromosome number)

11. Alterations in chromosome number
A trisomic cell has one extra chromosome (2n +1) = example: trisomy 21. (Polyploidy refers to the condition of having three homologous chromosomes rather then two)
A monosomic cell has one missing chromosome (2n - 1) = usually lethal except for one known in humans: Turner's syndrome (monosomy XO).

12. Alterations in chromosome number
The frequency of nondisjunction is quite high in humans, but the results are usually so devastating to the growing zygote that miscarriage occurs very early in the pregnancy.
If the individual survives, he or she usually has a set of symptoms - a syndrome - caused by the abnormal dose of each gene product from that chromosome.

13. Alterations in chromosome number

14. Human disorders due to chromosome alterations in autosomes
A. Down syndrome (trisomy 21): The result of an extra copy of chromosome 21. People with Down syndrome are 47, 21+. Down syndrome affects 1:700 children and severely alters the child's phenotype:

15. characteristic facial features, short stature; heart defects
susceptibility to respiratory disease, shorter lifespan
prone to developing early Alzheimer's and leukemia
often sexually underdeveloped and sterile, mental impairment

16. Karyotype:
Down's Syndrome is correlated with age of mother but can also be the result of nondisjunction of the father's chromosome 21.

17. Patau syndrome (trisomy 13): serious eye, brain, circulatory defects as well as cleft palate. 1:5000 live births. Children rarely live more than a few months

18. Edward's syndrome (trisomy 18): almost every organ system affected 1:10,000 live births. Children rarely live more than a few months.

19. Non-disjunction of the sex chromosomes
Klinefelter syndrome: 47, XXY males. Male sex organs; unusually small testes, sterile. Breast enlargement and other feminine body characteristics. Normal intelligence.

20. 47, XYY males: Individuals are somewhat taller than average and have below normal intelligence. At one time (~1970s), it was thought that these men were likely to be criminally aggressive, but this hypothesis has been disproven over time.

21. Trisomy X: 47, XXX females. 1:1000 live births - healthy and fertile - cannot be distinguished from normal female except by karyotype

22. Monosomy X (Turner's syndrome): 1:5000 live births; the only viable monosomy in humans. XO individuals are genetically female, however, they do not mature sexually during puberty and are sterile. Short stature and normal intelligence. (98% die before birth)

23. Gene mutations:
change in gene sequence that can change protein production.
These mutations are copied each time the DNA molecule is replicated.
Point mutations: substitution, deletion or addition of a single nucleotide
substitution: one nucleotide in a codon is replaced with a different nucleotide resulting in a different codon.
Deletion or insertion: shifts the entire code resulting in a nonsense message

24. Gene mutations

25. Barbara McClintock Discovered Jumping genes
discovered that genes move within a chromosome or to a new chromosome.
referred to as transposons: jump to new places when signaled
Acceptance of Jumping Gene theory
1951 McClintock presents her theory not well received because she used old style technology
1970 others observe the same phenomena as McClintock (using electron microscopes) accept her theory
use the concept of transposons to explain some evolution
also being used to analyze antibody production and cancer cell growth.

26. Jumping Genes Genes that move from chromosome to chromosome.
Can cause neighboring genes to become inactive or active

27. Human Genetic Disorders
Genetic Pedigree
It is a family tree for a trait
Allows us to trace genetic disorders

28. Sex Linked disorders: those carried in the sex chromosome
Usually carried on the x chromosome and are recessive.
Passed from mother to son.

29. Genetically Inherited Human Disorders
Autosomal recessive disorders: Show up only in the homozygous recessive person (aa) who inherits a recessive allele from both parents, who
were carriers (Aa xAa). (25% chance of this happening)

30. Autosomal recessive disorders
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.
Tay-Sachs: Enzyme that breaks down brain lipids is non-functional in homozygous recessives (tt). Buildup of lipids causes death by age 2-3.
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).
PKU Phenylketonuria 10,000 to 20,000 Caucasian or Oriental births. The incidence in African Americans is far less. genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. Untreated can result in an eczema-like rash, nervous system function to severe problems such as mental retardation and seizures.

31. Heterozygote advantage
For some disease alleles, being a heterozygote offers protection against another disease.
Examples:
Sickle cell disease: Ss carriers are resistant to malaria (note: 1:10, or 10% African-Americans are carriers Ss)
Cystic fibrosis: Cc carriers are resistant to cholera (note: 1:25, or 4% of caucasians is a carrier Aa).
Tay-Sachs: Tt carriers are thought to be more resistant to tuberculosis

32. Autosomal dominant disorders
child will show the phenotype if he / she receives just 1 allele from either parent. With just 1 parent affected, 50% chance of offspring being affected.

33. HETEROCHROMIA
Melaoncytes that are nt functoning
Mosaicisms: applied to an animal that has more than one cytogenetically-distinct population of cells
PIEBALDISM
Chimera:an individual having more than one genetically-distinct population of cells that originated from more than one zygote.
GEEP