Heredity notes

Heredity is the passing of phenotypic traits from parents to their offspring, either through asexual reproduction or sexual reproduction. This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve through the natural selection of specific phenotype traits. The study of heredity in biology is called genetics, which includes the field of epigenetics.
In humans, eye color is an example of an inherited characteristic: an individual might inherit the "brown-eye trait" from one of the parents.[1] Inherited traits are controlled by genes and the complete set of genes within an organism's genome is called its genotype.

The complete set of observable traits of the structure and behavior of an organism is called its phenotype. These traits arise from the interaction of its genotype with the environment. As a result, many aspects of an organism's phenotype are not inherited. For example, suntanned skin comes from the interaction between a person's phenotype and sunlight; thus, suntans are not passed on to people's children. However, some people tan more easily than others, due to differences in their genotype:[5] a striking example is people with the inherited trait of albinism, who do not tan at all and are very sensitive to sunburn.

Heritable traits are known to be passed from one generation to the next via DNA, a molecule that encodes genetic information. DNA is a long polymer that incorporates four types of bases, which are interchangeable. The sequence of bases along a particular DNA molecule specifies the genetic information: this is comparable to a sequence of letters spelling out a passage of text.  Before a cell divides through mitosis, the DNA is copied, so that each of the resulting two cells will inherit the DNA sequence. A portion of a DNA molecule that specifies a single functional unit is called a gene; different genes have different sequences of bases. Within cells, the long strands of DNA form condensed structures called chromosomes. Organisms inherit genetic material from their parents in the form of homologous chromosomes, containing a unique combination of DNA sequences that code for genes. The specific location of a DNA sequence within a chromosome is known as a locus. If the DNA sequence at a particular locus varies between individuals, the different forms of this sequence are called alleles. DNA sequences can change through mutations, producing new alleles. If a mutation occurs within a gene, the new allele may affect the trait that the gene controls, altering the phenotype of the organism.

However, while this simple correspondence between an allele and a trait works in some cases, most traits are more complex and are controlled by multiple interacting genes within and among organisms. Developmental biologists suggest that complex interactions in genetic networks and communication among cells can lead to heritable variations that may underlie some of the mechanics in developmental plasticity and canalization.

Recent findings have confirmed important examples of heritable changes that cannot be explained by direct agency of the DNA molecule. These phenomena are classed as epigenetic inheritance systems that are causally or independently evolving over genes. Research into modes and mechanisms of epigenetic inheritance is still in its scientific infancy, however, this area of research has attracted much recent activity as it broadens the scope of heritability and evolutionary biology in general.
DNA methylation marking chromatin, self-sustaining metabolic loops, gene silencing by RNA interference, and the three dimensional conformation of proteins (such as prions) are areas where epigenetic inheritance systems have been discovered at the organismic level.
Heritability may also occur at even larger scales. For example, ecological inheritance through the process of niche construction is defined by the regular and repeated activities of organisms in their environment. This generates a legacy of effect that modifies and feeds back into the selection regime of subsequent generations. Descendants inherit genes plus environmental characteristics generated by the ecological actions of ancestors.
Other examples of heritability in evolution that are not under the direct control of genes include the inheritance of cultural traits, group heritability, and symbiogenesis.These examples of heritability that operate above the gene are covered broadly under the title of multilevel or hierarchical selection, which has been a subject of intense debate in the history of evolutionary science

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Wild type gene

Wild type refers to the phenotype which is most common in nature. This generally refers to a phenotypic which is found in almost all “wild” members of a particular species. Eg, in gerbils, the brown color is the wild type. All other colors are rare in nature. When there is s clear wild type allele for a particular gene, that allele is often simply represented by a “+” rather than a letter (eg, brown = +; black = b). Another common way to designate a wild type is by using the symbol for the rare allele (usually recessive) with a “+” to represent the wild type (eg, brown = b+; black = b).
A balanced polymorphism exists when more than one common phenotype exists in a natural population of a particular species. The balance refers to the fact that the allelic frequencies for the traits do not change from generation to generation. Eg, eye color is a balanced polymorphism in modern human beings, the two common phenotypes being brown and blue. There was almost undoubtedly a time in the distant past, when all of our ancestors lived in the intense sunlight of Africa, when brown was the wild type human eye color. But in modern humans, that’s no longer true.

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All Genetic Term

Glossary of Terms
Molecular Biology, Genetics and Clinical Neurology

Laura Liscum, Stephen L. Sturley and Marc Patterson
(Compiled and edited by Cate Walsh Vockley)

Included here is a glossary of terms frequently used in molecular biology and neurobiology.  Much of it is jargon and will probably not be encountered in daily life, but nevertheless it will be found in the literature.  It is by no means complete, however it should help in finding explanations for most puzzling terms!

Alleles: Alternate forms of a gene at a specific location or locus; a single allele for each locus is inherited separately from each parent ( e.g., at the location for eye color genes, the inherited allele might result in blue or brown eyes).  A significant number of different alleles (forms) may exist for a single gene, with many alleles representing mutations that disrupt gene function and cause disease

Ataxia: Failure of muscular coordination; irregularity of muscle action.

Base sequence:  The order of nucleotide bases in a DNA molecule.

Brainstem:  The ‘stalk’ of brain tissue that connects the spinal cord, cerebellum and cerebral hemispheres.  Control of eye movements, breathing, heart rate, blood pressure and the nerves of the head and neck reside in the brainstem.  Brain death is defined by irreversible loss of the brainstem function.

Cataplexy:  A sudden loss of muscle tone, usually evoked by a strong stimulus such as laughter or anger.  Cataplexy is believed to represent a fragment of rapid eye movement (REM) sleep that intrudes into otherwise normal consciousness.  It correlates with dysfunction of the upper brainstem.

Cell:  The basic unite of all organisms.  Can be of several different types depending on function [e.g. macrophages (a type of blood cell), neuron (nerve cell), hepatocyte (liver cell) erythrocyte (red blood cell)]. The cell is separated from the external environment by the plasma membrane and within the cell is subdivided into organelles such as the nucleus, the endoplasmic reticulum, the golgi or the lysosome. 

Cholesterol: The most abundant sterol in mammalian cells.

Chromosomes:  The self-copying genetic structures of cells containing the cellular DNA that bears in its nucleotide sequence the genes or blueprints for cell function.  In prokaryotes (cells that do not have a nucleus), chromosomal DNA is circular, and the entire genome (all the genes in an organism) is carried on one chromosome.  Eukaryotic cell (with a nucleus) genomes consist of a number of chromosomes whose DNA is associated with different kinds of proteins.  

Cloning:  The process of producing a group of cells (clones), all genetically identical, from a single ancestor cell.  In recombinant DNA technology, the use of DNA manipulation procedures to produce multiple copies of a single gene or segment of DNA is referred to as cloning DNA.  More recently “cloning” has been used to describe the asexual production of whole organisms from a single somatic diploid cell (i.e. not a sperm or ovum but a cell that has a complete set of chromosome) e.g. “Dolly the sheep”

Coat protein: Proteins that coat vesicles and direct their trafficking or movement in cells.

Cortex:  The outer layer of any organ, as in the cerebral and cerebellar cortex.  In the brain, the cortex consists of neurons (grey matter)..

DNA (deoxyribonucleic acid):  The molecule that encodes genetic information.  The four nucleotides in DNA contain the bases: adenine (A), guanine (G), cytosine (C), and thiamine (T) held together by weak bonds between base pairs of nucleotides.  In nature, base pairs form only between A and T and between G and C; thus the base sequence of each single strand can be deduced from that of its paired or complimentary strand (like a mirror image).

DNA sequence:  The relative order of base pairs, whether in a fragment of DNA, a gene, a chromosome, or an entire genome.

Dystonia: disordered muscle tone.

Early Endosome: A vesicle that has just pinched off of the plasma membrane.

Endogenous: developing or coming from within an organism.

Endoplasmic reticulum: A network (reticulum) of membranes inside (endo) the cell soup
(plasm). The assembly line for protein and lipid synthesis.

Endosome: A vesicle (soma = body) that has pinched or budded off of the plasma membrane
into (endo) the cell.

Enzyme:  A protein that acts as a catalyst, speeding the rate at which a biochemical reaction proceeds (helps it happen more quickly and efficiently) but not altering the direction or nature of the reaction.  Example, sphingomyelinase

Eukaryote:  Cell or organism with membrane bound, structurally discrete nucleus and other well-developed subcellular compartments.  Eukaryotes include all organisms except viruses, bacteria, and blue-green algae.  Compare to prokaryote below.

Exogenous: developed or originating outside the organism.

Fatty acid: A major building block of cellular lipids.  It is a long carbon chain that ends in a
carboxylic acid (a chemical structure = -COOH)

Ganglioside: A sphingolipid with sugars attached.

Gene:  The fundamental physical and functional unit of heredity.  A gene is an ordered sequence of nucleotides located in a particular position on a particular chromosome that encodes a specific functional product (i.e., a protein or RNA molecule).  See gene expression.  Example NPC1, NPC2

Gene expression:  The process by which a gene’s coded information is converted into the structures present and operating in the cell.  Expressed genes include those that are transcribed (copied) into mRNA and then translated into protein and those that are transcribed into RNA but not translated into protein (e.g. transfer and ribosomal RNAs)

Gene Knockout:  Specific targeting of a gene by homologous recombination (pairing and rearrangement of 2 copies or alleles of a gene) commonly performed in mice.  Frequently, this is designed to produce a complete and specific loss of function of the gene. (See transgenic mice). 

Genotype: the genetic makeup of an individual; usually refers to the gene structure of a particular gene being analyzed.

Gene Product:  The biochemical material, either RNA or protein, resulting from expression of a gene. The amount of gene product is used to measure how active a gene is; abnormal amounts can be correlated with disease-causing alleles.  

Genetic Code:  The sequence of nucleotides, coded in triplets (codons) along the mRNA that determines that sequence of amino acids in protein synthesis.  The DNA sequence of a gene can be used to predict the mRna sequence, and the genetic code can in turn be
used to predict the amino acid sequence. 

Glycolipid: A lipid with sugar attached. 

Glycoprotein: A protein with sugar attached.

GM2 and GM3: Simple gangliosides that serve as building blocks for complex ones.

Golgi apparatus: An organelle that looks like a stack of membranes, containing enzymes that
add sugars to proteins and lipids. Also contains other protein modification enzymes.  The cell's
dessert buffet.

Homologies:  Similarities in DNA or protein sequences between individuals of the same species or among different species.

Hydrophilic: Loves water

Hydrophobic: Hates water.

Late endosome: A vesicle that pinched off of the plasma membrane a while ago.

Lipid: Molecules that prefer to be in chloroform rather than water (hydrophobic, or won’t
dissolve in water).

Lysosome: An organelle (soma = body) that contains enzymes that lyse (cut up) proteins, lipids,
nucleic acids, and sugars.  The cell's recycling center.

Membranes: A planar (flat) bilayer (two layers) of lipids.  Looks like an Oreo cookie, with hydrophilic heads facing out (the cookie part) and hydrophobic legs in the middle (the filling). All eukaryotic (i.e. higher) cells are separated from the external environment and subdivided by membranes.  This serves to protect or insulate the cells from extremes of pH (acidity/alkalinity), drying/desiccation, or salinity and to isolate toxic components into protected or non-lethal compartments within the cell.  Membranes are made up of phospholipid bilayers, which contain cholesterol and proteins. 

Metabolite: The product of a metabolic (enzymatic) reaction.

Mitochondrion: An organelle that uses glucose and fatty acids to make energy.  The cell's
Power plant.

Nucleus: An organelle that contains most of the cells genetic material (nucleic acid).  The cell's
cookbook.

Null: Completely missing.

Organelle: Little organ.  A compartment within the cell that contains proteins (i.e. enzymes) that
work together for a common purpose.

Permease:  A protein pump that permits efficient movement of molecules through membranes (see transporter). A protein that helps molecules permeate (cross) the membrane.

pH: A measurement of how acidic (like lemon juice) or basic (like baking soda) a solution is.

Phenotype: the outward appearance or physical symptoms of an individual.

Phospholipid:  Another building block of membranes which, along with cholesterol, that forms a barrier for the cell from the outside and also for sub-compartments of the cell. Has hydrophilic head and hydrophobic legs (the fatty acids). An important type of phospholipid is sphingomyelin.  Gangliosides are also types of phospholipids. 

Plasma membrane:  The outermost membrane of the cell which insulates or protects it from the environment.  It is made up of phospholipid, cholesterol and membrane protein (often pumps to allow passage of molecules through the barrier).

Protein:  A large molecule composed of one or more chains of amino acids in a specific order; the order is determined by the base sequence of nucleotides in the gene coding for the protein.  Proteins are required for the structure, function, and regulation of the body’s cells, tissues, and organs, and each protein has unique functions.  Examples are hormones, enzymes, and antibodies.

Rabs: A family of coat proteins.  Mammalian cells have at least 60 different Rab proteins.

Sequencing:  Determination of the order of nucleotides (base sequences) in a DNA or RNA molecule or the order of amino acids in a protein.  

Sphingolipid: A lipid that contains sphingosine.  Enriched in the brain.  Named after the Sphinx
because of their enigmatic nature.

Sphingomyelin:  A specific type of phospholipid and an important component of membranes, particularly the plasma membrane.  Sphingomyelin is acted on by the enzyme Sphingomyelinase, which is defective in NP A and B disease.  Cholesterol binds to Sphingomyelin in the plasma membrane.

Systemic: pertaining to or affecting the body as a whole.

Transporter:  A protein that permits or promotes movement within the cell or across membranes.  Can act as a permease or as a mediator of transport vesicle fusion events.

Vesicle: A small membrane-delimited sac that buds off of one membrane, carrying cargo, and
fuses with another.

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Quantitative traits

A quantitative or polygene trait is controlled by two or more different genes working in concert. Eg, hman skin color is controlled by between five and fifteen different genes, each with at least two different alleles. The skin phenotype of an individual is the product of all of the at least 10 alleles of these genes working together, plus the impact of environmental influence. The result of quantitative inheritance is generally that the trait doesn’t show discretely different phenotypes, but rather demonstrates a continuous variation in the species. Human skin color demonstrates this perfectly. There are no “categories” of human skin color, just a continuous spectrum from very pale to very dark.
Many quantitative traits are threshold traits. A threshold trait has basically only two expressions, even though it may be controlled by a number of genes working together. The cumulative effects of all of those genes (and often a significant amount of contribution from environmental factors) determines whether the phenotype will “cross the threshold” from one expression to the other. A probable example of a threshold trait in human beings is schizophrenia. It has been well established that heredity contributes significantly to the possibility that an individual will develop schizophrenia. Each of us inherits a certain level of “predisposition” in our genotypes. Environmental influences can also act to promote the onset of schizophrenia. If one inherits a genotype which contains a high level of genetic predisposition, it can take very little environmental contribution to cross the threshold and trigger the development of schizophrenia. However, if ones genetic predisposition is low, one may be able to accept a high level of environmental influence without developing the symptoms of schizophrenia.
Pliotropy refers to genes with multiple effects. For example, the white spotting gene in gerbils apparently also influences red blood cell count. Another simple example is that genes which influence characteristics of the fingers will also influence characteristics of the toes.

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Protein Sequence Alignment and Analysis

Amino acid sequence alignment andanalysis is centralto most biochemical and molecular biology applications. Although it shouldbepossible to retrieve all the information we need about a protein directly from its sequence, looking at a sequence without prior knowledge and experience is like reading a text in a foreign language: we may recognize the letters, but we do not understand the meaning and are unable to extract the information. Still, when proteins are concerned, we have learned to extract a substantial part of the information from detailed sequence analysis, using for example multiple sequence alignment. In a multiplesequencealignment a given sequence is compared to a group of evolutionary related sequences from other organisms. The pleasant fact is that we will always find a relatedprotein from some other organism. When we say "related" we mean that they belong to thesame family, the members of which usually perform a similar function in different organisms. We know that in such cases the main characteristic features of a protein sequence and the protein tertiary structure are conserved. Since conservation of function assumes that a certain number of amino acid residues within a protein family are conserved, weneedto have some instruments to assess the degreeof conservation of each sequence. To assist in the process, alignment techniques and scoring schemes for sequence alignment have been developed. Here I will discuss the basic concepts behindthese techniques and willprovide two examples to guide you in makingsequence alignment using resources available on the Internet. Since we focus here on structuralbioinformatics, the alignments we make will be interpreted in terms of the three-dimensionalstructure. We will also discuss what structural information may be identifiedin a sequence alignment, how to relate sequence and structuralinformation and how to make use of available structural data to make better sequence alignment.

When making a sequence alignment we need to take into account several factors. For example, we needto understand the effect of replacements of one amino acidby another (amino acid substitutions) in different sequences. Thus, some substitutions are conservative, i.e., they will not introduce any substantial disturbances in the protein structure, while others may have dramatic effect on thestructure and function of the protein in question andthey are normally rather rare. To account for the different types of substitutions, there are specially designed so called substitution matrices, which can be used for makinga correct alignment and for calculating the score of the alignment. Structural information may also be used to assist us in making a correct alignment, for example in understanding the effect of amino acid substitutions.

There will also be two guided examples, which will make use of the sequence alignment and analysis resources available at the Expasy server. In some cases the alignment may be easy to make, while in others, for example when we align multidomain proteins, or when there is a large number of insertions and deletions, extra attention is required. Structuralinformation, and particularly protein secondary structure, may provide valuable insights into the effects of various replacements, insertions and deletions. The results form these tutorials will be used later in homology modeling, which will follow in the chapter dedicated to modeling.

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Chromosomal aberrations

Chromosomal aberrations (or abnormalities) refer to the group of conditions where there is an anomaly, either in the number or the structure of chromosomes in a cell. This might be seen as a large-scale mutation, occurring above the level of change in nucleotide sequences. A number of genetic diseases are linked to chromosomal aberrations.

Numerical abnormalities are typically referred to with the suffix -somy. The usual situation in a diploid cell is disomy: having two copies of each chromosome. When a homologous pair of chromosomes either loses or gains a chromosome, this disrupts the total complement of chromosomes in that cell such that it is no longer a multiple of the monoploid number (x). This phenomenon is called aneuploidy. A monosomy is the loss of a chromosome, while trisomy, tetrasomy, etc. involve gaining chromosomes. Examples of genetic diseases where aneuploidy has occurred are trisomy 21, the presence of three copies of chromosome 21, or Down's Syndrome, and monosomy X, the loss of an X chromosome in a human female, or Turner's Syndrome.

Possible structural aberrations in chromosomes are diverse, and include:

• Deletions, where part of a chromosome is lost completely. This loss of genetic material may have devastating impacts on the individual: known human disorders include Wolf-Hirschhorn Syndrome, caused by a deletion on chromosome 4, and Jacobsen syndrome, caused by a deletion at the terminus of the long arm of chromosome 11.

• Duplications, where part of a chromosome is copied, causing an addition of genetic material (the copy may be a paralog). An example human disease is Charcot-Marie Tooth Disease type 1A, which may be caused by a gene duplication on chromosome 17.

• Translocations, where part of a chromosome is excised and moved to another chromosome. Translocations may be subdivided into two types: reciprocal translocation, where two chromosomes exchange segments, and Robertsonian translocation, where an entire chromosome attaches to another at its centromere, forming a dicentric chromosome. In humans, Robertsonian translocations only occur between the acrocentric chromosomes 13, 14, 15, 21 and 22; any Robertsonian translocation involving chromosome 21 may cause Down's Syndrome in the offspring of that individual.

• Inversions, where a portion of chromosome is excised, flips around, and is reinserted back-to-front. Comes in two types: paracentric and pericentric.

• Rings, where a portion of chromosome breaks off and forms an independent circular structure, either with or without the loss or gain of genetic material

• Isochromosomes, where a chromosome arm is lost and replaced by an exact mirror image of the remaining arm.

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Mendel's Law

law of segregation

T principle stating that during the production of gametes the two copies of each hereditary factor segregate so that offspring acquire one factor from each parent.

 Law of independent assortment.

 principle stating that the laws of chance govern which particular characteristics of the parental pairs will occur in each individual offspring.

 law of dominance.

 The principle stating that one factor in a pair of traits dominates the other in inheritance unless both factors in the pair are recessive.

Mendelian Genetics Definitions


Allele - one alternative form of a given allelic pair; tall and dwarf are the alleles for the height of a pea plant; more than two alleles can exist for any specific gene, but only two of them will be found within any individual.
Allelic pair - the combination of two alleles which comprise the gene pair.

Homozygote - an individual which contains only one allele at the allelic pair; for example DD is homozygous dominant and d d is homozygous recessive; pure lines are homozygous for the gene of interest.

Heterozygote - an individual which contains one of each member of the gene pair; for example the Dd heterozygote.
Genotype - the specific allelic combination for a certain gene or set of genes.

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