Human Genetic Variation by National Institute of Health - HTML preview

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part of many important laboratory techniques

developmental disorder that results when the

such as polymerase chain reaction and

forebrain of the embryo fails to divide and form

Southern blotting.

the right and left halves of the brain. The disorder

produces a single-lobed brain structure and severe

identical twins: Identical twins are also known

skull and facial abnormalities. The deformities

as monozygotic twins. They result from the

often cause babies to die before birth. In mild

fertilization of a single egg that splits in two.

cases, babies are born with near-normal brain

Identical twins share all of their genes and are

development and facial abnormalities involving

always of the same sex. In contrast, fraternal, or

cleft lip or cleft palate.

dizygotic, twins result from the fertilization of

two separate eggs during the same pregnancy.

homologous recombination: Homologous

They share half their genes, just like any other

recombination is a type of genetic recombination

siblings. Fraternal twins can be of the same or

that occurs during meiosis (the formation of

different sexes.

egg and sperm cells). Paired chromosomes from

the male and female parent align so that similar

in situ hybridization: In situ hybridization is a

DNA sequences from the paired chromosomes

laboratory technique in which a single-stranded

cross over each other. Crossing over results in a

DNA or RNA sequence called a probe is allowed

shuffl ing of genetic material and is an important

to form complementary base pairs with DNA or

cause of the genetic variation seen among offspring.

RNA present in a tissue or chromosome sample.

The probe has a chemical or radioactive label

attached to it so that its binding can be observed.

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inherited: An inherited trait is one that is

LOD score: LOD stands for “logarithm of the

genetically determined. Inherited traits are passed

odds.” In genetics, the LOD score is a statistical

from parent to offspring according to the rules

estimate of whether two genes, or a gene and a

of Mendelian genetics. Most traits are not strictly

disease gene, are likely to be located near each

determined by genes, but rather are infl uenced by

other on a chromosome and are therefore likely

both genes and environment.

to be inherited together. A LOD score of 3 or

higher is generally understood to mean that

insertion: Insertion is a type of mutation

two genes are located close to each other. In

involving the addition of genetic material.

terms of signifi cance, a LOD score of 3 means

An insertion mutation can be small, involving a

the odds are 1,000 to 1 that the two genes are

single extra DNA base pair, or large, involving a

linked and, therefore, inherited together.

piece of a chromosome.

lymphocyte: A lymphocyte is a type of white

intron: An intron is a portion of a gene that does

blood cell that is part of the immune system.

not code for amino acids. In the cells of plants

There are two main types of lymphocytes: B cells

and animals, most gene sequences are broken

and T cells. The B cells produce antibodies that

up by one or more introns. The parts of the gene

attack invading bacteria, viruses, and toxins.

sequence that are expressed in the protein are

The T cells destroy the body’s own cells that

called exons because they are expressed, while

have themselves been taken over by viruses

the parts of the gene sequence that are not

or become cancerous.

expressed in the protein are called introns

because they come in between the exons.

lyonization: Lyonization is commonly known

as X-inactivation. In mammals, males receive

karyotype: A karyotype is an individual’s

one copy of the X chromosome while females

collection of chromosomes. The term also refers

receive two copies. To prevent female cells from

to a laboratory technique that produces an image

having twice as many gene products from the

of an individual’s chromosomes. The karyotype is

X chromosomes as males, one copy of the X

used to look for abnormal numbers or structures

chromosome in each female cell is inactivated.

of chromosomes.

In placental mammals, the choice of which X

chromosome is inactivated is random, whereas

knockout: A knockout typically refers to an

in marsupials, it is always the paternal copy

organism that has been genetically engineered

that is inactivated.

to lack one or more specifi c genes. Scientists

create knockouts (often in mice) so that they

lysosome: A lysosome is a membrane-bound

can study the impact of the missing genes and

cell organelle that contains digestive enzymes.

learn something about the genes’ function.

Lysosomes are involved with various cell

processes. They break down excess or worn-

linkage: Linkage is the close association of

out cell parts. They may be used to destroy

genes or other DNA sequences on the same

invading viruses and bacteria. If the cell is

chromosome. The closer two genes are to each

damaged beyond repair, lysosomes can help it

other on the chromosome, the greater the

self-destruct in a process called programmed

probability that they will be inherited together.

cell death, or apoptosis.

locus: A locus is the specifi c physical location of

a gene or other DNA sequence on a chromosome,

like a genetic street address. The plural of locus

is “loci.”

51

Glossary

Human Genetic Variation

mapping: Mapping is the process of making a

Mendel performed thousands of crosses with

representative diagram cataloging the genes and

garden peas at his monastery during the middle of

other features of a chromosome and showing

the 19th century. Mendel explained his results by

their relative locations. Cytogenetic maps are

describing two laws of inheritance that introduced

made using photomicrographs of chromosomes

the idea of dominant and recessive genes.

stained to reveal structural variations. Genetic

maps use the idea of linkage to estimate the

messenger RNA (mRNA): Messenger RNA

relative locations of genes. Physical maps, made

(mRNA) is a single-stranded RNA molecule that

using recombinant DNA (rDNA) technology,

is complementary to one of the DNA strands

show the actual physical locations of landmarks

of a gene. The mRNA is an RNA version of the

along a chromosome.

gene that leaves the cell nucleus and moves to

the cytoplasm where proteins are made. During

marker: A marker is a DNA sequence with a

protein synthesis, an organelle called a ribosome

known physical location on a chromosome.

moves along the mRNA, reads its base sequence,

Markers can help link an inherited disease

and uses the genetic code to translate each three-

with the responsible genes. DNA segments

base triplet, or codon, into its corresponding

close to each other on a chromosome tend

amino acid.

to be inherited together. Markers are used to

track the inheritance of a nearby gene that has

metagenomics: Metagenomics is the study of a

not yet been identifi ed but whose approximate

collection of genetic material (genomes) from a

location is known. The marker itself may be a

mixed community of organisms. Metagenomics

part of a gene or may have no known function.

usually refers to the study of microbial communities.

meiosis: Meiosis is the formation of egg and

metaphase: Metaphase is a stage during the

sperm cells. In sexually reproducing organisms,

process of cell division (mitosis or meiosis).

body cells are diploid, meaning they contain two

Usually, individual chromosomes cannot

sets of chromosomes (one set from each parent).

be observed in the cell nucleus. However,

To maintain this state, the egg and sperm that

during metaphase of mitosis or meiosis,

unite during fertilization are haploid, meaning

the chromosomes condense and become

they each contain a single set of chromosomes.

distinguishable as they align in the center of the

During meiosis, diploid cells undergo DNA

dividing cell. Metaphase chromosomes are used

replication followed by two rounds of cell

during the karyotyping procedure used to look

division, producing four haploid sex cells.

for chromosomal abnormalities.

Mendel, Johann (Gregor): Gregor Mendel was an

microarray technology: Microarray technology

Austrian monk who in the 19th century worked

is a developing technology used to study the

out the basic laws of inheritance, even before the

expression of many genes at once. It involves

term “gene” had been coined. In his monastery

placing thousands of gene sequences in known

garden, Mendel performed thousands of crosses

locations on a glass slide called a gene chip. A

with garden peas. Mendel explained his results by

sample containing DNA or RNA is placed in

describing two laws of inheritance that introduced

contact with the gene chip. Complementary

the idea of dominant and recessive traits.

base pairing between the sample and the gene

sequences on the chip produces light that is

Mendelian inheritance: Mendelian inheritance

measured. Areas on the chip producing light

refers to patterns of inheritance of organisms that

identify genes expressed in the sample.

reproduce sexually. The Austrian monk Gregor

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microbiome: A microbiome is all of the genetic

Monosomy can be partial if a portion of the

material found within an individual microbe such

second chromosome copy is present. Monosomy,

as a bacterium, fungal cell, or virus. It also may

or partial monosomy, is the cause of some human

refer to the collection of genetic material found

diseases such as Turner syndrome and Cri du

in a community of microbes that live together.

Chat syndrome.

microsatellite: Microsatellite sequences are

mouse model: A mouse model is a laboratory

repetitive DNA sequences usually several base

mouse used to study some aspect of human

pairs in length. Microsatellite sequences are

physiology or disease. A variety of different model

composed of noncoding DNA and are not parts

organisms are used in this regard, but mice are

of genes. They are used as genetic markers to

especially useful because they share mammalian

follow the inheritance of genes in families.

features with humans and suffer from many of the

same diseases. A large number of mouse models

missense mutation: A missense mutation is

have been created by selective breeding and genetic

when the change of a single base pair causes

engineering to target specifi c human diseases.

the substitution of a different amino acid in the

resulting protein. This amino acid substitution

mutagen: A mutagen is a chemical or physical

may have no effect, or it may render the protein

phenomenon, such as ionizing radiation, that

nonfunctional.

promotes errors in DNA replication. Exposure to

a mutagen can produce DNA mutations that cause

mitochondria: Mitochondria are membrane-

or contribute to diseases such as cancer.

bound cell organelles (mitochondrion, singular)

that generate most of the chemical energy

mutation: A mutation is a change in a DNA

needed to power the cell’s biochemical reactions.

sequence. Mutations can result from DNA copying

Chemical energy produced by the mitochondria

mistakes made during cell division, exposure to

is stored in a small molecule called adenosine

ionizing radiation, exposure to chemicals called

triphosphate (ATP). Mitochondria contain

mutagens, or infection by viruses. Germ line

their own small chromosome(s). Generally,

mutations occur in eggs and sperm and can be

mitochondria, and therefore mitochondrial

passed on to offspring, while somatic mutations

DNA, are inherited only from the mother.

occur in body cells and are not passed on.

mitochondrial DNA: Mitochondrial DNA is

nanotechnology: Nanotechnology is the science of

the small circular chromosome found inside

manipulating matter on the atomic and molecular

mitochondria. Mitochondria are the organelles in

scales to solve problems. Nanotechnology is a

cells where energy is produced. The mitochondria,

developing applied science that has the potential

and thus mitochondrial DNA, are passed from

to make signifi cant contributions to many

mother to offspring.

fi elds, including engineering, computer science,

and medicine.

mitosis: Mitosis is a cellular process that

replicates chromosomes and produces two

newborn screening: Newborn screening is

identical nuclei in preparation for cell division.

testing performed on newborn babies to detect

Generally, mitosis is immediately followed by

a wide variety of disorders. Typically, testing is

the equal division of the cell nuclei and other

performed on a blood sample obtained from a

cell contents into two daughter cells.

heel prick when the baby is two or three days

old. In the United States, newborn screening is

monosomy: Monosomy is the state of having

mandatory for several different genetic disorders,

a single copy of a chromosome pair instead

though the exact set of required tests differs

of the usual two copies found in diploid cells.

from state to state.

53

Glossary

Human Genetic Variation

noncoding DNA: Noncoding DNA sequences

nucleic acid: Nucleic acids are an important class

do not code for amino acids. Most noncoding

of macromolecules found in all cells and viruses.

DNA lies between genes on the chromosome

The functions of nucleic acids have to do with the

and has no known function. Other noncoding

storage and expression of genetic information.

DNA, called introns, is found within genes.

Deoxyribonucleic acid (DNA) encodes the

Some noncoding DNA plays a role in the

information the cell needs to make proteins. A

regulation of gene expression.

related type of nucleic acid, called ribonucleic

acid (RNA), comes in different molecular forms

nondirectiveness: Nondirectiveness refers to

that participate in protein synthesis.

the nature of the genetic counseling process.

According to the principle of nondirectiveness,

nucleolus: The nucleolus is a region found

the genetic counselor has the responsibility to

within the cell nucleus concerned with producing

provide the client with accurate information

and assembling the cell’s ribosomes. Following

about a test or outcome but should remain

assembly, ribosomes are transported to the cell

neutral and not try to infl uence the decisions

cytoplasm, where they serve as the sites for

made by the client.

protein synthesis.

nonsense mutation: A nonsense mutation is

nucleopore: A nucleopore is one of a series of

the substitution of a single base pair that leads to

small holes found in the nuclear membrane.

the appearance of a stop codon where previously

The nucleopore serves as a channel for

there was a codon specifying an amino acid. The

transporting nucleic acids and proteins into

presence of this premature stop codon results

and out of the cell nucleus.

in the production of a shortened, and likely

nonfunctional, protein.

nucleosome: A nucleosome is the basic repeating

unit of eukaryotic chromatin. In a human cell,

northern blot: Northern blot is a laboratory

about six feet of DNA must be packaged into a

technique used to detect a specifi c RNA sequence

nucleus with a diameter less than a human hair.

in a blood or tissue sample. The sample RNA

A single nucleosome consists of about 150 base

molecules are separated by size using gel

pairs of DNA sequence wrapped around a core of

electrophoresis. The RNA fragments are transferred

histone proteins. The nucleosomes are arranged

out of the gel to the surface of a membrane. The

like beads on a string. They are repeatedly folded

membrane is exposed to a DNA probe labeled

in on themselves to form a chromosome.

with a radioactive or chemical tag. If the probe

binds to the membrane, then the complementary

nucleotide: A nucleotide is the basic building

RNA sequence is present in the sample.

block of nucleic acids. RNA and DNA are

polymers made of long chains of nucleotides.

nuclear membrane: A nuclear membrane is a

A nucleotide consists of a sugar molecule

double membrane that encloses the cell nucleus.

(either ribose in RNA or deoxyribose in DNA)

It serves to separate the chromosomes from the

attached to a phosphate group and a nitrogen-

rest of the cell. The nuclear membrane includes

containing base. The bases used in DNA are

an array of small holes, or pores, that permit the

adenine (A), cytosine (C), guanine (G), and

passage of certain materials, such as nucleic acids

thymine (T). In RNA, the base uracil (U)

and proteins, between the nucleus and cytoplasm.

takes the place of thymine.

54

nucleus: A nucleus is a membrane-bound

peptide: A peptide is one or more amino acids

organelle that contains the cell’s chromosomes.

linked by chemical bonds. The term also refers

Pores in the nuclear membrane allow molecules

to the type of chemical bond that joins the amino

to pass into and out of the nucleus.

acids together. A series of linked amino acids is

a polypeptide. The cell’s proteins are made from

oncogene: An oncogene is a mutated gene that

one or more polypeptides.

contributes to the development of a cancer. In

their normal, unmutated state, oncogenes are

personalized medicine: Personalized medicine

called proto-oncogenes, and they play roles in the

is an emerging practice of medicine that uses

regulation of cell division. Some oncogenes work

an individual’s genetic profi le to guide decisions

like putting your foot down on the accelerator of

about the prevention, diagnosis, and treatment

a car, pushing a cell to divide. Other oncogenes

of disease. Knowledge of a patient’s genetic profi le

work like removing your foot from the brake while

can help doctors select the proper medication or

parked on a hill, also causing the cell to divide.

therapy and administer it using the proper dose or

regimen. Personalized medicine is being advanced

open reading frame: An open reading frame is a

through data from the Human Genome Project.

portion of a DNA molecule that, when translated

into amino acids, contains no stop codons. The

pharmacogenomics: Pharmacogenomics is a

genetic code reads DNA sequences in groups of

branch of pharmacology concerned with using

three base pairs, which means that a double-

DNA and amino acid sequence data to inform

stranded DNA molecule can read in any of six

drug development and testing. An important

possible reading frames—three in the forward

application of pharmacogenomics is correlating

direction and three in the reverse. A long open

individual genetic variation with drug responses.

reading frame is likely part of a gene.

phenotype: A phenotype is an individual’s

organ: In biology, an organ (from the Latin

observable traits, such as height, eye color, and

“organum,” meaning an instrument or tool) is

blood type. The genetic contribution to the

a collection of tissues that structurally form a

phenotype is called the genotype. Some traits are

functional unit specialized to perform a particular

largely determined by the genotype, while others

function. Your heart, kidneys, and lungs are

are largely determined by environmental factors.

examples of organs.

phosphate backbone: A phosphate backbone is

organelle: An organelle is a subcellular structure

the portion of the DNA double helix that provides

that has one or more specifi c jobs to perform in

structural support to the molecule. DNA consists

the cell, much like an organ does in the body.

of two strands that wind around each other like a

Among the more important cell organelles are

twisted ladder. Each strand has a backbone made

the nuclei, which store genetic information;

of alternating sugar (deoxyribose) and phosphate

mitochondria, which produce chemical energy;

groups. Attached to each sugar is one of four

and ribosomes, which assemble proteins.

bases—adenine (A), cytosine (C), guanine (G), or

thymine (T). The two strands are held together by

pedigree: A pedigree is a genetic representation

bonds between the bases, with adenine forming

of a family tree that diagrams the inheritance of

a base pair with thymine and cytosine forming a

a trait or disease though several generations. The

base pair with guanine.

pedigree shows the relationships between family

members and indicates which individuals express

or silently carry the trait in question.

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