Chapter 6

What are ways to determine if your baby has down syndrome?

-Amniocentesis: fetal cells are obtained from amniotic fluid -CVS: fetal cells are obtained from chorion of the placenta -NIPGD: a new approach to deriving cells from maternal circulation. Fetal cells are cultured, and the karyotype can be determined by cytogenetic analysis.

The Bar Mutation in Drosophila

-Duplications result in Bar-eyed flies that have narrow, slit-like eyes versus normal oval- shaped eyes. -16A region on the X chromosome responsible for eye shape is duplicated in Bar flies and triplicated in double Bar flies.

Familial Down Syndrome

-In familial Down syndrome, one of the parents contains a 14/21, D/G translocation. That is one parent has the majority of the G-group chromosome 21 translocated to one end of the D-group chromosome 14. -This individual is phenotypically normal but has only 45 chromosomes. -During meiosis, one-fourth of the gametes have two copies of chromosome 21: a normal chromosome and a second copy translocated to chromosome 14. Fertilization of gamete by a standard haploid gamete results in an embryo with 46 chromosomes but three copies of chromosome 21, exhibiting Down syndrome.

rRNA

-Organisms have multiple copies of the ribosomal RNA genes (rRNA). It is needed to support protein synthesis -Multiple copies of genes code for rRNA (rDNA)

Duplication

-Repeated segment of a chromosome -arise through unequal crossing over between synapsed chromosomes during meiosis or through a replication error prior to meiosis  -Duplications may result in: 1. gene redundancy. 2. phenotypic variation. 3. genetic variability during evolution.

Fragile X Syndrome (Martin-Bell Syndrome)

-people bearing a folate-sensitive site on the X chromosome exhibit this syndrome. -is the most common form of inherited mental retardation, affecting about 1 in 4000 males and 1 in 8000 females, and is a dominant trait - the trait is not fully expressed. for females; Thirty percent are mentally retarded. for males; 80 percent are mentally retarded. -A gene that spans the fragile site may be responsible for this syndrome, this gene is called FMR-1.

types of inversions

A paracentric inversion does not include the centromere A pericentric inversion includes the centromere

There are two primary ways in which the structure of chromosomes can be altered:

1. The total amount of genetic information in the chromosome can change. Due to Deletions and Duplications 2. The genetic material remains the same, but is rearranged. Due to Inversions and Translocations (reciprocal and nonreciprocal) In most instances, these structural changes are due to one or more breaks along the chromosomal axis followed by loss or rearrangement. Breakages can occur spontaneously, or Exposure to chemicals or radiation can increase these breakages Alternations that occur in gametes are heritable.

Polyploidy originates in two ways

1. the addition of one or more sets of chromosomes identical to the haploid complement of the same species (autopolyploidy) 2. the combination of chromosome sets from different species as a consequence of interspecific matings (allopolyploidy)

autotetraploids

4n -Because they have an even number, autotetraploids (4n) are theoretically more likely to be found in nature than autotriploids.are more likely to produce balanced gametes. -produce 2n gametes Tetraploids arise when chromosomes have replicated and the parent cell fails to divide and instead enters interphase: the chromosome number will have duplicated. Supported by the idea that tetraploid cell can be produced experimentally from diploid cells: Experimentally done by applying heat or cold shock to diploid cells undergoing meiosis or by applying colchicine to somatic cells undergoing mitosis

Down syndrome critical region (DSCR)

A critical region of chromosome 21 contains the genes that are dosage sensitive in this trisomy and are responsible for many of the phenotypes

The Link between Fragile Sites (on autosomes) and Cancer

A link between an autosomal fragile site and lung cancer was reported in 1996. The gene FHIT located within the FRA3B fragile site on p arm on chromosome 3 is often altered or missing in cells taken from individuals with lung cancer. Further studies have revealed that the normal protein product of this gene is absent in cells of many other cancers. Found within another fragile site FRA16D on chromosome 16 is the WWOX gene, which has been implicated in many human cancers. It is either lost or genetically silenced by methylation. The active gene behaves as a tumor suppressor, recognizing cancer cells and inducing apoptosis.

Origin of chromosome 21 for Down Syndrome

Down syndrome most frequently occurs due to nondisjunction of chromosome 21 during meiosis. Failure of paired homologs to disjoin during either anaphase 1 or 2 may lead to gametes with the n+1 chromosome composition. Seventy-five percent occur during Meiosis I. Fertilization with a normal gamete creates the trisomic condition. -Ninety-five percent of Down syndrome occurs from either the sperm or the egg carrying the extra chromosome 21 in ovum.

Autopolyploidy

Each additional set of chromosomes is identical to the parent species. So triploids are AAA, tetraploids are AAAA, and so on. A=haploid set of chromosomes of any organism Autopolyploid flowers and fruits are often increased in size, making such varieties of greater horticultural or commercial value.

inversion heterozygotes

Organisms with one inverted chromosome and one noninverted chromosome -can't do regular synapsis in meiosis because of inverted chromosome So synapsis of inverted chromosomes requires an inversion loop If crossing over does not occur within the inverted segment of the inversion loop, the homologs will segregate resulting in two normal and two inverted chromatids distributed in gametes. If crossing over does occur in the inversion loop, abnormal chromatids are produced. A large heterozygous inversion will result in greater numbers of genes that are duplicated or deleted when crossing over occurs.

In addition to Down syndrome only two other trisomies survive to term but manifest severe malformations and early lethality. What are they called?

Patau syndrome 47,13+ and Edward syndrome 47,18+

monosomy

The loss of one chromosome (2n - 1) may have severe phenotypic effects. Monosomy for the X chromosome occurs in humans Monosomy for any of the autosomes is usually not tolerated in humans and other animals but better tolerated in the plant kingdom. Death may occur due to lethals being unmasked, or a single recessive gene may be insufficient to provide life-sustaining function for the organism (haploinsufficiency).

Trisomy

Trisomy (2n + 1 chromosomes) is usually more viable than the loss of a chromosome (monosomy) Trisomies for autosomes (for Drosophila and humans0 have severe effects and are usually lethal during development. Trisomic plants are viable, but their phenotype may be altered: Datura Rice larger chromosomes are more of a problem

Which of the following statements about the products produced when nondisjunction occurs during meiosis I is true?

Two products of the second meiotic division have both the maternal and paternal chromosomes of a set and the other two products have none for that set.

aneuploidy

Variations in chromosome number are known as aneuploidy when an organism gains or loses one or more chromosomes and does not have an exact multiple of the haploid set 2n +/- x chromosomes kinds; Monosomy 2n-1 Disomy 2n Trisomy 2n+1

Deletion

When a chromosome breaks in one or more places and a portion of it is lost, the missing piece is referred to as a deletion (or a deficiency). near one end (terminal deletion), or from the interior of the chromosome (intercalary deletion) For synapsis to occur between a chromosome with a large intercalary deletion and a normal complete homolog, the unpaired region of the normal homolog must "buckle" out into a deletion or compensation loop Although small deletions usually have no adverse effect, this can sometimes occur.

position effect.

When genes change their position in a chromosome, their expression and thus phenotype may change. Inversions and translocations change the gene order along chromosomes and may initially cause little or no loss of genetic information or deleterious effects, aside from alterations of phenotype due to position effects.

Karyotype analysis of spontaneously aborted fetuses reveal that

at least 6 percent of all conceptions contain an abnormal chromosome complement. A large percent of fetuses demonstrating chromosomal abnormalities are aneuploids. Gametes lacking a single chromosome are functionally impaired to a serious degree or the embryo dies early.

Autotriploids

can arise if a diploid gamete (due to nondisjunction of all chromosomes) is fertilized by a haploid gamete. This produces a zygote with three sets of chromosomes -Diploids crossed with tetraploids under experimental conditions can also give triploids.

Chromosomal mutations/abberations

changes from normal two haploid sets of chromosomes. includes: a change in the total number of chromosomes. the deletion or duplication of genes or segments of a chromosome. rearrangements of the genetic material within or among chromosomes. These changes can result in some form of phenotypic variation and may even be lethal.

euploidy

complete haploid sets of chromosomes are present. multiples of n includes; diploidy polyploidy and triploidy

How many chromosomes would be found in an allopolyploid plant if its parents had diploid numbers of 4 and 6 respectively?

diploid number of 5

A cross between a tetraploid and a diploid member of the same species will produce offspring that can undergo sexual reproduction. True or false

false: Offspring from this cross would be triploid and produce gametes with an uneven number of homologous chromosomes, making sexual reproduction unlikely.

The Role of Gene Duplication in Evolution

gene duplication is essential to the origin of new genes during evolution. -The duplicated copy can acquire many mutational changes over extended periods. Over long evolutionary periods, the duplicated gene may change sufficiently so that its product assumes a divergent role in the cell. The new function may impart an "adaptive" advantage to organisms, enhancing their fitness. Support is provided by the discovery of genes that have a substantial amount of their organization and DNA sequence in common but whose gene products are distinct. Trypsin, chymotrypsin, myoglobin, and various forms of hemoglobin are so similar that members of each pair of genes probably arose from a common ancestor through gene duplication. During evolution, the related genes diverged sufficiently that their products became unique. -transition from invertebrates to vertebrates may have involved duplication of entire genomes.

FMR-1

has a trinucleotide repeat sequence CGG. a hugh number of repeats can express the fragile-X syndrome. -Normal individual: 6-54 repeats; "carriers": 55-230 -Fragile-X syndrome: more than 230 repeats, which causes the gene to become methylated and results in gene inactivation. -The number of CGG repeats continues to increase in future generations (genetic anticipation), becoming more severe in successive generations provided it comes from the mother. Thus a carrier male may transmit a stable chromosome to his daughter who may transmit an unstable chromosome with an increased number of repeats to her offspring. Their grandfather was the source of the original chromosome. Expansion from the carrier status to the syndrome status occurs only during the transmission of the gene by the maternal parent, not the paternal parent.

polyploidy

if more than two sets of haploid chromosomes are present. A triploid has 3n chromosomes. A tetraploid has 4n chromosomes. A pentaploid has 5n chromosomes. -Common in plant species -Research has shown that as polyploidy increases, gene expression either increases or decreases at tenfold. Two genes that encode G1 cyclins are expressed when ploidy increases. The polyploid cell stays in the G1 phase longer and grows to a larger size.

inversion

involves a rearrangement of the linear gene sequence rather than the loss of genetic information. -turned 180 degrees within a chromosome. -An inversion requires two breaks in the chromosome and subsequent reinsertion of the inverted segment An inversion may arise from chromosomal looping Homozygous inversions pair normally during meiosis, so crossing over does not produce inviable gametes. Loop formation allows pairing within inverted regions of homologous chromosomes regardless of whether the centromere is included in the inversion.

Robertsonian translocation

involves breaks at the extreme ends of the short arms of two nonhomologous acrocentric chromosomes.The small segments are lost and the larger segments fuse at their centromeric region. This type of translocation produces a new large submetacentric or metacentric chromosome. -Familial Down syndrome is an example

reciprocal translocation

involves the exchange of segments between two nonhomologous chromosomes. -If the exchange includes internal chromosome segments, four breaks are required, two on each chromosome. -has an unusual synapsis configuration during meiosis results in rearrangement of genetic material not loss of genetic material. -genetically unbalanced gametes are produced but not result from crossing over. two possible segregation patterns: one that leads to a normal and a balanced gamete (called alternate segregation) one that leads to gametes containing duplications and deficiencies (called adjacent segregation) Results in semisterility, which has a big impact on reproductive fitness, thus playing a big role in evolution. Partial monosomy or trisomy leading to birth defects

Gene amplification

is a mechanism to increase the rDNA that codes for rRNA. In some cells, particularly oocytes, even the normal amplification of rDNA is insufficient to provide adequate amounts of RNA needed to construct ribosomes. In Xenopus laevis (an amphibian), 400 copies of rDNA are present per haploid and are found in a single area of the chromosome called the nucleolar organizer region (NOR). Selectively replicated to further increase rDNA copies

Translocation

is the movement of a chromosomal segment to a new location in the genome.

Fragile sites

looked like gaps at first because parts of chromosomes failed to stain. -are more susceptible to chromosome breakage when cells are cultured in the absence of certain chemicals such as folic acid. -Could be regions along the chromosome where chromatin is not tightly coiled. -There is a strong association between fragile sites and mental retardation.

Chromosomal variation can arise from ____and how?

nondisjunction: because chromosomes fail to segregate during meiosis 1 and 2, chromosomes don't distribute evenly to gametes. Fertilization of abnormal gametes with normal gametes results in zygotes with three members (trisomy) or only one member (monosomy of this chromosome).

paracentric inversion crossover:

one recombinant chromatid is dicentric (two centromeres). one is acentric (lacking a centromere).

Down Syndrome: Trisomy 21

only human autosomal trisomy where people last longer than a year past birth -1/800 live births -250,000 individuals currently in United States with Down syndrome -Down syndrome has 12 to 14 characteristics, and affected individuals express 6 to 8 on average (Figure 6-2). Prominent epicanthic fold in each eye Flat face, round head, short stature with protruding tongue Short, broad hands with characteristic palm and fingerprint pattern Mental retardation, average life span 50 years. -Children are prone to respiratory disease and heart malformations. Show a higher incidence of leukemia (20 times higher) Death in older individuals often due to Alzheimer's disease, which usually occurs earlier than in normal population. -People with syndrome have decreased risk in some cancers because of an extra copy of the DSCR1 which seems to be associated with decreased risk of some cancers. Approximately 10% reduction -as the age of childbearing women exceeds 45, the probability of Down syndrome births continues to increase substantially. Down syndrome is caused by a random error—nondisjunction of chromosome 21, thus the disorder is not expected to be inherited. Nevertheless, Down syndrome occasionally runs in families (familial Down syndrome). Translocation of bottom part of chromosome 21 onto another chromosome

Cri du Chat Syndrome in Humans

results from a segmental deletion of a small terminal portion of the short arm of chromosome 5 -is a segmental deletion -is 46,5p-, meaning that the person has all 46 chromosomes but that some or all of the p arm of one member of the chromosome 5 pair is missing -The condition is not inherited but results from the sporadic loss of chromosomal material in gametes. -Severity of the syndrome varies with length of deletion. Symptoms include an eerie cry similar to a cat's meowing and anatomic malformations, including gastrointestinal and cardiac complications. -Those affected have abnormal glottis and larynx development and are often mentally retarded.

allotetraploid/ amphidiploid

results from hybridization of two closely related species. -the hybrid organism can become sterile if soem or all of the a and b chromosomes are not homologous and can't synapse in meiosis. If hybrid goes through a natural or induced chromosomal doubling, two copies of all a and b chromosomes, they will pair during meiosis and create a tetraploid AABB. It contains four haploid genomes derived from separate species. can also be produced by somatic cell hybridization. -can be found in nature ex: cotton