| Relationship between genes and chromosomes | Genes are located on chromosomes
[REFERENCE PICTURE] |
| Sutton and Boveri? Chromosome theory of inheritance? | - Mendel’s proposed “hereditary units” were only theoretical in 1860
- Soon, biologists saw parallels between chromosome behavior and the behavior of the proposed factors
- Around 1902, Sutton and Boveri and others independently noted these parallels and began to develop the chromosome theory of inheritance |
| Thomas Hunt Morgan | - The first solid evidence associating a specific gene with a specific chromosome came in the early 1900s from the work of Thomas Hunt Morgan
- His early experiments provided convincing evidence that the chromosomes are the location of Mendel’s heritable factors
- For his work, Morgan chose to study Drosophila melanogaster, a common species of fruit fly |
| Characteristics that make fruit flies a convenient organism for genetic studies | - They produce many offspring
- A generation can be bred every two weeks
- They have only four pairs of chromosomes |
| Wild type | Morgan noted wild type, or normal, phenotypes that were common in the fly populations |
| mutant phenotypes | - Traits alternative to the wild type are called mutant phenotypes
- The first mutant Morgan discovered was a fly with white eyes instead of the wild-type red eyes |
| Generations within Morgan's experiment | - In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type)
- The F1 generation all had red eyes
- The F2 generation showed a 3:1 red to white eye ratio, but only males had white eyes |
| Morgan's reasoning on why the generations ended up the way they were | - Morgan reasoned that the white-eyed mutant allele must be located on the X chromosome
- Female flies have two X chromosomes (XX) while males have one X and one Y (XY)
- Morgan’s finding supported the chromosome theory of inheritance |
| Why was Morgan's discovery important? | Morgan’s discovery of a trait that correlated with the sex of flies was key to the development of the chromosome theory of inheritance |
| Sex chromosomes | - Humans and other mammals have two types of sex chromosomes: a larger X chromosome and a smaller Y chromosome
- A person with two X chromosomes usually develops anatomy we associate with the “female” sex
- “Male” properties are associated with the inheritance of one X and one Y
- The X-Y system is not the only chromosomal system of sex determination |
| How certain chromosomes lead to the development of certain things? SRY? | - Short segments at the ends of the Y chromosomes are homologous with the X, allowing the two to behave like homologs during meiosis in males
- In mammals, a gene on the Y chromosome called SRY (sex-determining region on the Y) is responsible for development of the testes in an embryo |
| Sex-linked gene? Y-linked genes? X-Linked genes? | - A gene that is located on either sex chromosome is called a sex-linked gene
- Genes on the Y chromosome are called Y-linked genes
- Many Y-linked genes are related to sex determination
- Only 78 genes, coding for about 25 proteins, have been identified on the human Y chromosome
- Genes on the X chromosome are called X-linked genes; the human X chromosome contains about 1,100 genes
- X chromosomes have genes for many characters unrelated to sex |
| Pattern of inheritance for X-linked genes | - For a recessive X-linked trait to be expressed:
- a female needs two copies of the allele (homozygous)
- a male needs only one copy of the allele (hemizygous)
- X-linked recessive disorders are much more common in males than in females |
| Some disorders caused by recessive alleles on the X-Chromosomes in Humans | - Color blindness (mostly X-linked)
- Duchenne muscular dystrophy
- Hemophilia |
| Barr body? Mosaic? | - In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development
- The inactive X condenses into a Barr body
- If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character |
| Inactivation of an X chromosome | - Inactivation of an X chromosome involves modification of the DNA and proteins bound to it called histones
- A part of the chromosome contains several genes involved in the inactivation process
- One of the genes there becomes active only on the chromosome that will be inactivated
- The gene is called XIST (X-inactive specific transcript) |
| Linked genes | - Each chromosome has hundreds or thousands of genes (except the Y chromosome)
- Genes that are located on the same chromosome tend to be inherited together and are called linked genes |
| Morgan's experiments with linkage | - Morgan did experiments with fruit flies to see how linkage affects inheritance of two characters
- Morgan crossed flies that differed in traits of body color and wing size
- The first cross was a P generation cross to generate F1 dihybrid flies
- The second was a testcross |
| Results from Morgan's experiments with linkage | - The resulting flies had a much higher than expected proportion of the combination of traits seen in the P generation flies (parental phenotypes)
- He concluded that these genes do not assort independently and reasoned that they were on the same chromosome |
| Genetic recombination | - Nonparental phenotypes were also produced in the testcross, suggesting that the two traits could be separated sometimes
- This involves genetic recombination, the production of offspring with combinations of traits differing from either parent
- A 50% frequency of recombination is observed for any two genes on different chromosomes
- The genetic findings of Mendel and Morgan relate to the chromosomal basis of recombination |
| Parental types | Offspring with a phenotype matching one of the parental (P) phenotypes are called parental types |
| Recombinant types or Recombinants | Offspring with nonparental phenotypes (new combinations of traits) are called recombinant types, or recombinants |
| Crossing over | - Morgan observed that although some genes are linked, nonparental allele combinations are still produced
- He proposed that some process must occasionally break the physical connection between genes on the same chromosome
- That mechanism was the crossing over of homologous chromosomes |
| Genetic variation | - Recombinant chromosomes bring alleles together in new combinations in gametes
- Random fertilization increases even further the number of variant combinations that can be produced
- This abundance of genetic variation is the raw material upon which natural selection works |
| Alfred Sturtevant? Genetic map? | - Alfred Sturtevant, one of Morgan’s students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosome
- Sturtevant predicted that "the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency" |
| Linkage map | A linkage map is a genetic map of a chromosome based on recombination frequencies |
| Map units | - Distances between genes can be expressed as map units; one map unit represents a 1% recombination frequency
- Map units indicate relative distance and order, not precise locations of genes |
| Recombinant frequency and Gene locations | - Genes that are far apart on the same chromosome can have a recombination frequency near 50%
- Such genes are physically linked, but genetically unlinked, and behave as if found on different chromosomes |
| How were recombinant frequencies and linkage maps used? | - Sturtevant used recombination frequencies to make linkage maps of fruit fly genes
- They found that the genes clustered into four groups of linked genes (linkage groups)
- The linkage maps, combined with the fact that there are four chromosomes in Drosophila, provided additional evidence that genes are located on chromosomes |
| What leads to miscarriages | - Large-scale chromosomal alterations in humans and other mammals often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders
- Plants tolerate such genetic changes better than animals do |
| Nondisjunction | - In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis
- As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy |
| Aneuploidy | - Aneuploidy results from the fertilization of gametes in which nondisjunction occurred
- Offspring with this condition have an abnormal number of a particular chromosome |
| Monosomic zygote | A monosomic zygote has only one copy of a particular chromosome |
| Trisomic zygote | A trisomic zygote has three copies of a particular chromosome |
| Polyploidy | - Polyploidy is a condition in which an organism has more than two complete sets of chromosomes
- Triploidy (3n) is three sets of chromosomes
- Tetraploidy (4n) is four sets of chromosomes
- Polyploidy is common in plants, but not animals
- Polyploids are more normal in appearance than aneuploids |
| Breakage of a chromosome leads to four types of changes in chromosome structure: | - Deletion removes a chromosomal fragment
- Duplication repeats a segment
- Inversion reverses orientation of a segment within a chromosome
- Translocation moves a segment from one chromosome to another |
| Human Disorders Due to Chromosomal Alterations | - Alterations of chromosome number and structure are associated with some serious disorders
- Some types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyond
- These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy |
| Down Syndrome (Trisomy 21) | - Down syndrome is an aneuploid condition that results from three copies of chromosome 21
- It affects about one out of every 830 children born in the United States
- The frequency of Down syndrome increases with the age of the mother, a correlation that has not been explained |
| Aneuploidy of Sex Chromosomes | - Nondisjunction of sex chromosomes produces a variety of aneuploid conditions
- Klinefelter syndrome is the result of an extra chromosome in a male, producing XXY individuals
- About one in 1,000 males is XYY; these males do not exhibit any syndrome
- XXX females occur with a frequency of about one in 1,000
- They are healthy, with no unusual physical features, though they are at risk for learning disabilities
- Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans |
| Disorders Caused by Structurally Altered Chromosomes | - The syndrome cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5
- A child born with this syndrome is severely intellectually disabled and has a catlike cry; individuals usually die in infancy or early childhood
- Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations
of chromosomes |
| Exceptions to Mendelian genetics | - There are two normally occurring exceptions to Mendelian genetics
- One exception involves genes located in the nucleus, and the other involves genes located outside the nucleus
- In both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritance |
| Genomic imprinting | - For a few mammalian traits, the phenotype depends on which parent passed along the alleles for those traits
- Such variation in phenotype is called genomic imprinting
- Genomic imprinting involves the silencing of certain genes depending on which parent passes them on
- Most imprinted genes are on autosomes
- The mouse gene for insulin-like growth factor 2 (Igf2) was one of the first imprinted genes to be identified
- Only the paternal allele of this gene is expressed |
| What causes imprinting? | - It seems that imprinting is the result of the methylation (addition of —CH3 groups) of cysteine nucleotides
- Genomic imprinting may affect only a small fraction of mammalian genes
- Most imprinted genes are critical for embryonic development |
| Extranuclear genes (or cytoplasmic genes) | - Extranuclear genes (or cytoplasmic genes) are found in organelles in the cytoplasm
- Mitochondria, as well as chloroplasts, and other plant plastids carry small circular DNA molecules
- Extranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg
- The first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant |
| Results of defects in mitochondrial genes | - Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems
- For example, mitochondrial myopathy and Leber’s hereditary optic neuropathy |
| Possibilities in avoiding passing along mitochondrial disorders | - It may be possible to avoid passing along mitochondrial disorders
- The chromosomes from the egg of an affected mother could be transferred to an egg of a healthy donor, generating a “two-mother” egg
- This egg could then be fertilized by sperm from the prospective father and transplanted to the womb of the prospective mother |
