ch 16

Fragile X syndrome

Fragile X syndrome

FMR-1: fragile X mental retardation-1

Normal individuals:

29 CGG repeats (6-54), Normal transmitting males (20% persons with a Fragile X chromosome, but is normal), their daughters, and female carries: 55-200 copies of CGG, Males and females with fmr-1 syndrome: 200-1300 copies

Euploid

An organism or a cell has one complete set of chromosomes or an exact multiple of completes sets

Aneuploid

An organism or a cell has a chromosomes number that is not an exact multiple of the haploid set of chromosomes, The nondisjunction of one or more chromosomes during meiosis I or meiosis II typically is responsible for generating gametes with abnormal numbers of chromosomes

Trisomy-21 (Down syndrome)

Down syndrome can also result from RT

Robertsonian Translocation Down's Syndrome

Trisomy-13 (Patau syndrome), Trisomy-18 (Edwards syndrome)

Triploidy

also called triploidy, is a chromosomal disorder in which a fetus has three copies of every chromosome instead of the normal two. If this occurs in only some cells, it is called mosaic triploidy and is less severe.

Amphidiploids

an individual that is a hybrid of two different species and that possesses more than two sets of chromosomes

THE OPERON CONCEPT, lac OPERON, Arabinose OPERON, Tryptophan OPERON

Transcription of DNA à RNA

Translation of RNA →Protein

the process whereby mRNA is converted into proteins by ribosomes. Translation occurs in ribosomes, which are cellular structures made of proteins and ribosomal RNA (rRNA). Here, mRNA is converted into amino acid sequences, forming polypeptides.

Stability of mRNA

depends on cis-acting sequences within the mRNA (mostly in the 3′-untranslated region, UTR) and on trans-acting RNA-binding proteins (Martin and Ephrussi, 2009)

Posttranslational modification of proteins

covalent changes to proteins that involve the breaking and forming of chemical bonds

François Jacob, Jacques Monod

The Nobel Prize in Physiology or Medicine 1965 "for their discoveries concerning genetic control of enzyme and virus synthesis" Institute Pasteur, Paris, France

The Lactose Operon in E. coli

Monod et al isolated many Lac- mutants, that is, bacterial cells unable to utilize lactose

Polytene chromosomes

Special kinds of chromosome found in certain tissues (e.g. the salivary glands in the larval stages) of insects, Consist of chromatid bundles resulting from repeated cycles of chromosome duplication without nuclear or cell division, a process called endoreduplication, The homologous chromosomes are tightly paired (synapsed), therefore, the observed number of polytene chromosomes per cell is reduced to half the diploid number of chromosomes

Deletions

Part of a chromosome is missing

Pseudodominance (Drosophila scarlet gene)

The deletion of the dominant allele of a heterozygote results in the appearance of the phenotype of the recessive allele

Deletion Mapping

Red bar show the bands removed by deletions, w: white, rst: roughest, fa: facet

Deletion cri-du-chat syndrome (OMIM 123450)

A partial deletion of the short arm of chr 5, Children with cri-du-chat syndrome are severely mentally retarded, have a number of physical abnormalities, and cry with a sound like the mew of a cat, 1 infant in 50,000 live births

Duplication

A chromosomal mutation that results in the doubling of a segment of a chromosome

Duplications can have unique phenotypic effects

Alfred Sturtevant and Thomas Morgan (1920s)

Duplications play a critical role in evolution of multiple genes with related functions

Hemoglobin molecules contain two copies of each of two different subunits: the a-globin polypeptides and b-globin polypeptides, The genes for each of the a-globin polypeptides are clustered together on one chromosome and the genes for each of the b-globin polypeptides are clustered together on another, The gene sequences for all a-globin are similar, as are the sequences for the b-globin, Each assembly of genes evolved from a different ancestral gene by duplication and subsequent divergence in the sequences of the duplicated genes

Inversion (In)

A chromosomal mutation that results when a segment of chromosome is excised and reintegrated at an orientation 180 degrees from the original orientation, Pericentric In: include the centromere, Paracentric In: does not include the centromere

Paracentric Inversion

A single crossover within paracentric inversion loop

Pericentric Inversion

A single crossover within pericentric inversion loop

Translocations

Large-scale mutations, There is a change in position of chromosome segments, Usually there is no gain or loss of genetic material

Evidence of the association of genetic recombination with chromosomal exchange in corn

C: colored, c: colorless, Wx: amylose amylopectin, wx: amylopectin

Evidence of the association of genetic recombination with chromosomal exchange in Drosophila

Cytological markers

Reciprocal Translocations

a chromosomal abnormality where segments of two non-homologous chromosomes exchange pieces of genetic material with each other, resulting in a rearrangement of DNA but with no net gain or loss of genetic information

Meiosis in a translocation heterozygote without crossover

the two copies of chromosome 21 fail to segregate and end up in the same ovule.

Chromosomal Mutations and Tumors

Many human malignant tumors have chromosomal mutation, The most common class of chromosomal mutation associated with cancer is translocation, e.g. chronic myelogenous leukemia, Some tumors (epithelial tumors of the ovary, lung, and pancreas and many sarcomas (connetive-tissure tumors)) have complex patterns of chromosomal mutations

Philadelphia chromosome

c-abl: encodes a protein tyrosine kinase, bcr: breakpoint cluster region, bcr/c-abl: oncogene, always active even in the absence of growth factor, Gleevec®: inhibit the enzymatic activity of the protein kinase encoded by bcr/c-abl, In clinical trials, 98% of patients had a complete disappearance of leukemic blood cells

Position Effect

Change of phenotype due to the change of position of a gene in the genome (e.g. inversions or translocation)

Fragile Sites and Fragile X Syndrome

Fragile sites: gaps, narrowings, or unstained areas in some regions of chromosome, Spontaneous break at a fragile site, resulting in deletion of the chromosome distal to the site