CH.5: Pathophysiology

Expressivity

referes to the manner in which the gene is expressed in teh phenotype, which can range from mil to severe

penetrance

represents the ability of a gene to express its function. The percentage in a population with a particular genotype in which that genotype is phenotypically manifested.

RNA

Made up of a long string of nucleotides. However it is different because is is a single stranded rather than double-stranded molecule. Second, the sugar in each nucleotide of RNA is ribose instead of deoxyribose. Third, the pyrimidine base thymine in DNA is replaced by uracil in RNA.

Types of RNA

Messenger RNA, Ribosomal RNA, and Transfer RNA all the types of RNA are synthesized in the nucleus by RNA polymerase enzyme and then moved into the cytoplasm, where protein synthesis takes place.

Transcriptions

Occurs in the cell nucleus and involves the synthesis of RNA from a DNA template. Genes are transcribed by enzymes called RNA polymerase that generate a single-stranded RNA identical in sequence (with the exception of U in place of T) It is initiated by the assembly of a transcription complex composed of RNA polymerase.

Regulation of gene expression

only about 2% of the genome encodes instructions for synthesis of proteins. most occur at transcription level. involves a complex set of interrelationships among different levels of control including RNA transcription and post translational processing.

Gene dosage studies

involve measuring enzymes activity. Autosomal genes are normally arranged in pairs, and normally both are expressed. If both alleles are present and both are expressed, the activity should be 100% if one gene pair is missing on 50% activity.

Polygenetic inheritance

involves multiple genes and multifactorial inheritance which involves multiple genes as well as environmental factors, are less predictable.

Cell division

involves the duplication of the chromosomes. Duplication of chromosomes in somatic cells lines involves mitosis.

Posttranslational processing

involves the proper folding of the newly synthesized polypeptide chain into its unique three-dimensional conformation.

AUG

is a part of the initiation of start signal as well as the codon for the AA methionine.

Production of proteins

is accomplished by 1.) the transcription of the DNA code for assembly of the protein onto messenger RNA. 2.)The translation of the code from messenger RNA and assembly of the protein by ribosomal RNA in the cytoplasm, and 3.) The delivery of the Amino acids needed for protein synthesis to ribosomal RNA by transfer RNA.

Genetic code

is determined by the arrangement of the nitrogen bases of the 4 nucleotides.

Mitochondrial DNA

is inherited from the mother by her offspring. It is a double-Stranded closed circle containing 37 genes, 24 of which are needed for mitochondrial DNA translation and 13 of which are needed for oxidative metabolism.

Multifactorial inheritance

is similar to polygenic inheritance in that multiple alleles at different loci affect the outcome; includes environmental effects on genes.

Genetic information

is stored in a stable macromolecule called DNA

meiosis

limited to replicating germ cells and results in formation of a single set of 23 chromosomes. Results from the formation of gametes to reproductive cells.

XY Chromosome

male specific region

Dominant trait

one expressed in either a homozygous or a heterozygous paring.

Recessie trait

one expressed only in a homozygous pairing

Punnett square

shows all possible combinations for transmissions of a singe gene trait.

Mendelian

single gene, patterns of inheritance include autosomal dominant dan recessive traits that are transmitted from parents to their offspring.

Chromatin

Because of their large size, the DNA double helices are packaged as a coiled structure.

Codon

There are 64 different combinations but only 20 amino acids re used in protein synthesis.

Meiosis II

These cells contain 23 double stranded chromosomes (2 chromatids) of each of the two daughter cells from meiosis I divide at their centromeres.

Messenger RNA

carries instructions for proteins synthesis, obtained from the DNA molecule, into the cytoplasm. -Template for protein synthesis.

Gene imprinting

certain gene exhibited a "parent of origin" type of transmission in which the parental genomes do not always contribute equally in development of an individual. Approximately 100 genes exhibit gene imprinting.

Backbone of DNA

consist of alternating groups of sugar and phosphoric acid, with the paired bases projecting inward from the sides of the sugar molecule.

Haplotype map

focuses on identifying the slight variations in the human genome that impact on a individual's susceptibility to disease and response to environmental factors such as microbes, toxins, and drugs.

Genetic Variability

human genome sequence is almost exactly (99.9%) the same in all people. It is the small variation (.10%) in gene sequence is though to accounts for the individual differences.

Complmentary genes

in which each gene is mutually dependent on the other

multiple alleles

in which more than one allele affects the same trait. (ABO blood group)

collaborative gene

in which two different genes influencing the same trait interact to produce a phenotype neither gene alone could produce.

Heterozygotes

Have different alleles (Aa) at a gene locus

Meiosis I

Homologous chromosomes pair up forming a synapsis or tetrad There is crossing over which allows for new combinations of genes (pairing of chromosomes, chiasma formation, pulling apart of double structured chromosomes, anaphase) These cells contain 46 double structured chromosomes

Haplotype Mapping

Identify the common pattern of DNA sequence variations in the human genome would be possible. It is anticipated that the HapMap Project will provide a useful tool for disease diagnosis and management.

Somatic cell hybridization

Involves the fusion of human somatic cells with those of a different species to yield a cell containing the chromosomes of both species.

Situ hybridization

Involves the use of specific sequences of DNA or RNA to locate genes that do not express themselves in cell culture.

Purine bases

Adenine (A) and guanine (G) which have two.

Cytogenetics

the study of the structure and numeric characteristic of the cell's chromosome.

Genetic maps

they use linkage studies to estimate the distance between chromosomal landmarks

Genome

total genetic content.

Gene isolation and cloning

used in recombinant DNA technology rely on the fact that the genes of all organisms, from bacteria throughout mammals, are based on a similar molecular organization.

Function of DNA in controlling Cel Function

-The information needed for the control of cell structure and function lis embedded in the genetic information encoded in the stable DNA molecule. -Although every cell in the body contains the same genetic information, each cell type uses only a portion of the information, depending on the structure and function.

Pedigree

A graphic method for portraying a family history of an inherited trait. It is constructed from a carefully obtained family history and is useful for tracing the pattern of inheritance for a particular trait.

Double Helix and Base Pairing

A precise complementary pairing of purine and pyrimidine bases occurs in the double-stranded DNA molecule in which A is paired with T and G is paired with C. Before cell division, the two strands of the helix separates and a complementary molecule is duplicated next to each original strand. Two strands become four.

Gene repression

A process by which a regulatory gene acts to reduce or prevent gene expression.

physical maps

Are similar to a surveyor's map. They make use of cytogenetic and molecular techniques to determine the actual, physical locations of genes on chromosomes.

Nucleotides

DNA is composed of this. - Consist of phosphoric acid, a five-carbon sugar called deoxyribose, and one of four nitrogenous bases.

Zygote

DNA's stable structure also allows the information to survive the many processes of reduction devisor involved in gamete (ovum and sperm) formation, the fertilization process, and the mitotic cell division involved in the formation of a new organism form the single-celled fertilization called a zygote.

Proteome

Defines teh complete set of proteins encoded by a genome.

Mutations

Errors in duplication of DNA occur. Result from the substitution of one base pair for another, the loss or addition of one or more base pairs, or rearrangements of base pairs. Many of these occur spontaneously, whereas others occur because of environmental agents, chemicals, and radiation.

XX Chromosome

Female specific region

Genetic code

Four bases-Guanine, adenine, cytosine, and thymine- make up the alphabet of the genetic code. A sequence of three of these bases forms a triplet code (codon)

Transmission of genetic information

From one generation to the next is vested in genetic material transferred from each parent at the time of conception

DNA

Our genetic information is stored here. It is an extremely stable molecule. Needed to direct the function of our cells, determine our appearance and how we respond to our environment, and serve as the unit of inheritance that is passed on from generation to generation. Contains instructions for proteins synthesis.

Homozygotes

Persons in whom the two alleles of a given pair are the same (AA or aa)

From Genes to Proteins

RNA, through the process of transcription and translation, that is responsible for the actual assembly of the products.

Transfer RNA

Reads the instruction and delivers the appropriate AA to the ribosome. The physical structure in the cytoplasm where protein synthesis takes place.

Pharmaceutical application

Recombinant DNA technology has also made it possible to produce proteins that have therapeutic properties. One of the first products to be produced was human insulin.

Recombinant DNA

Refers to a combination fo DNA molecules that are not found all together in nature. There is technology to make it possible to identify the DNA sequence in a gene.

phenotype

Refers to the recognizable traits: physical or biochemical, associated with a specific genotype.

Cloning

Requires cutting a DNA molecule apart, modifying and reassembling its fragments and producing copies of the modified DNA and its mRNA, and its gene product.

Endonucleases

Several repair mechanisms exist, and each depends on this specific enzyme. Recognize local distortions of the DNA helix, cleave the abnormal chain, and remove the distorted region. the gap is then filled when the correct DNA is created by a polymerase.

RNA interference Technology (RNAi)

Stop genes from making unwanted disease proteins. A naturally occurring process in which small pieces of double-stranded RNA suppress gene expression.

Mendel Second Law

The alleles from the different gene loci segregate independently and recombine randomly in the zygote.

Mitosis

The cell cycle process in which nongerm cells are replicated. It provides a way for the body to replace cells that have a limited life span (skin and blood) each daughter cell receives a par of 23 chromosomes.

Linkage studies

assume that genes occur in a linear array along the chromosomes. During meiosis the paired chromosomes of the diploid germ cell exchange genetic material because of the crossing-over phenomenon. When two inherited traits occur together at a rate greater than would occur by chance alone.

Chromosome

The genome is distributed here. -most genetic information of a cell is organized, stored and retrieved here. -Each human somatic cell (other than gametes: sperm and ovum) has 23 pairs of different chromosomes, with one member of the pair derived from the individual's mother and the other from the father. -The last pair consist of the sex.

Translational factors

The initiation and translation of RNA transcript is controlled by this. They bind to specific DNA regions and function to regulate gene expression of the many different types of cells in the body.

Mendel laws

The main feature of inheritance is predictability (the likelihood of the occurrence or recurrence of a specific trait)

RNA

The molecular link between DNA code of genes and the amino acid code of proteins. -Uracil (U) replaces thymine (T) as one of the pyrimidine bases.

Translation

The process of protein synthesis. the genetic code is translated into the production language needed for polypeptide assembly. occurs in the cytoplasm of the cell using the mRNA template. proteins are made from a standard set of AA.

Proteomics

The study of the proteome, uses highly sophisticated technologic methods to examine the molecular and biochemical events in a cell.

Genetic Mapping

This is the assignment of genes to specific chromosomes or parts of the chromosome.

DNA fingerprinting

This technique is based in part on those techniques used in recombinant DNA technology and on those originally used in medical genetics to detects slight variations in the genomes of different individuals. (Chromosomal DNA, Digest with restriction endonucleases, To DNA fragments, separate fragments into a gel electrophoresis, Denature and transfer DNA to nitrocellulose paper, then incubate with probe, wash nd pre from autobiography to observe labeled DNA bands)

Pyrimidine bases

Thymine (T) and cytosine (C), which have one nitrogen ring.

Ribosomal RNA

Translates the instructions and provides the machinery needed for protein synthesis. Is a clover-shaped molecule. its function is to deliver the activated form of an AA to the protein that is being synthesized in the ribosomes.

Mendel First Law

Two alleles from a gene locus separate so that each germ cell receives only one allele from each pair.

Gene therapy

Two main approaches are used in gene therapy transferred genes can replace defective genes or they can selectively inhibit deleterious genes. there are moral and ethical issues involved along with the problems with techniques that cannot direct the inserted DNA to attach to a particular chromosomes or supplant an existing gene by knocking it out of place.

Hybridization studies

Two somatic cells from different species, when grown together in the same culture, occasionally fuse to form a new hybrid cells. two types: Somatic cell hybridization and Situ hybridization

Carrier

a person who is heterozygous for a recessive trait and dos not manifest the trait.

Example of Gene imprinting

are teh transmissions of the mutations in Prader Willi and Angelman syndromes. both syndromes exhibit mental retardation as a common feature. both have a deletion in chromosome 15. When inherited from the mother: angel man when inherited from the father: Prader-Willi resulted.

Alleles

are the alternating forms of a gene

Units of inheritance

are the genes, and the pattern of single-gene expression can often be predicted using the medel laws of genetic transmission.

Gene

the degree to which a gene or particular group of genes is active. are the fundamental unit of information storage in the cell. they determine they types of proteins and enzymes made by the cell and therefore control inheritance and day to day cell function. Transmit information contained in the DNA molecule as a codon.

Genotype

the genetic information stored in the base sequence triplet code.

Locus

the position of a gene on a chromosome.