Scientists love to specialize -- it’s exciting and rewarding to develop
expertise in a chosen field. Your peers all speak a common language and
you feel comfortable in that environment. Just don’t try to communicate
with an expert from some other field!
The genealogist who is
researching family medical history can be confronted with an array of
obsolete medical and quasi-medical terms which can be very bewildering,
especially as many of these represent long-abandoned concepts about the
causes or treatments of human illnesses. Definitions have to be assessed
in the context of the historical era, the way in which the symptoms
presented and the customs of the times. A very useful reference of
obsolete medical terminology was written by Jeanette L. Jerger. It’s a
lexicon of medical terms that were used in past years. Published by
Heritage Books, it’s entitled A Medical Miscellany for Genealogists. From
ague to Zwischentrager, the book is a fascinating and valuable source
for obscure descriptions of illness.
FISH AND CHIPS
These
problems seem insignificant, though, when compared to the vast array of
scientific terms encountered when researching in the new and sometimes
intimidating field of genetic genealogy. Take, for example, the common
terms “fish and chips.” When Marshall Field employed a genealogist to
travel to England for two years and pursue his family’s pedigree, the
gentleman probably spent a fair amount of time in the pubs sampling the
local brews and munching on fish and chips. But to the molecular
biologist, FISH stands for fluorescence in situ hybridization in which
DNA probes labeled with fluorescent dye are used to study biological
specimens to find molecular genetic events, such as gene deletion,
chromosome translocation or aneuploidy. CHIPS have also assumed a new
meaning, referring to microarray methods of analysis using cells
containing gene fragments to predict the outcome of DNA-related diseases
and helping clinicians to pick out the most appropriate methods of
treatment.
It’s apparent that molecular genealogy is the language
of the present and the foreseeable future future as well. DNA’s
features are expressed in complex terminology that is quite familiar to
the geneticist but may be puzzling to a genealogist who cringes at the
mention of a chromosome. Even using as non-technical approach as
possible, these concepts require appropriate scientific definitions and
descriptions. We offer a short selection of words, pharases and
abbreviations which pervade the current literature, especially when
dealing with the medical applications of molecular biology. This list is
by no means all-inclusive. Acronyms proliferate faster than rabbits,
but we hope you’ll find it useful to refresh your memory about a
confusing array of terms used in a rapidly expanding science.
GENOSPEAK
FOR GENEALOGISTS
Adenine: Purine base designated by “A” --
one of 4 base molecules in DNA.
Allele: Genes can be in
several forms, or alleles at a single locus, or marker, on a chromosome.
If similar alleles are present in a pair of chromosomes, the person is homozygous.
Differing alleles make one heterozygous. In Y-chromosome
genealogical studies, repeating units, STR’s, are measured and recorded
for comparison with other males.
AMH: Atlantic Modal Haplotype
-- 6 markers; most common haplotype in Western Europe.
Amino
acid: Any of a class of 20 molecules which combine to make
proteins.
Antigen: Proteinaceous product detectable by
immunological methods employing matching antibodies.
-ase: Suffix
describie enzyme functions, e.g., lipase, dealing with fats.
Association
studies: Seeking a version of a gene which varies between affected
and non-affected individuals.
Autoradiogram (autorad): X-ray
film recording, e.g., as used to display polymorphic DNA fragments
present in mother, child and the alleged father.
Autosome: Any
chromosome other than sex or mitochondrial chromosomes. Humans have 22
pairs of autosmes (numbered 1-22), l pair of sex chromosomes.
B-DNA:
A naturally occurring form of DNA within cells.
Beta-DNA: A
branched form of DNA.
Bacteriophage: A virus which infects
certain bacteria, using host cell components in its reproduction.
Base:
Human DNA consists of 4 bases: adenine (A), cytosine (C), guanine
(G) and thymine (T), derived from either purine or pyrimidine.
Base
pairs: Complementary bases pair up via hydrogen bonds to form DNA
in “complementary strands.” Base-pairing occurs between purines and
pyrimidines, e.g., A to T and G to C.
Base sequence: Order of
nucleotides in a DNA molecules, e.g. AGTACGT.....
Bayes’ theorum: Statistical
means of assessing the relative probability of two alternative
possibilities, based upon acquired information. Can be applied to
parentage testing.
Bipolar disorder: Manic-depressive
psychosis.
BRCA1, BRCA2: Mutated genes associated with some
types of heritable breast, ovarian and other cancers.
Carrier: Person
(usually symptomatic) having recessive mutated gene plus its normal
allele. Also can refer to autosomal dominant conditions, denoting people
who have inherited predisposition(s) conferred by mutations.
Centromere:
Constricted portion near center of a chromosome having a
significant role in cell division.
Chromosome: Threadlike DNA
structure, consisting of the nucleotides adenine (A), guanine (G),
thymine (T) and cytosine (C), carrying linear sequenced genetic
information. Nucleated human cells have 23 pairs, including 22 pairs of
autosomes and 2 sex chromosomes.
Chromosome translocation: Abnormalitites
which occur when chromosomes exchange portions, or in reciprocal
translocation. Or they may fuse, called “centric fusion.” Translocation
can occur in cancer. In chronic myelogenous leukemia, a balanced
chromosome translocation occurs (Philadelphia chromosome).
Clone
(n): Genetically identical genes, or organisms derived from a
single ancestor. Clone (v): Molecular cloning involves isolating a gene
of DNA and inserting it into a cloning vector, which could be bacterial,
viral or a yeast cell. When this grows, it makes multiple copies useful
for research.
Complementary sequences of DNA: Double-stranded
DNA paired up according to certain rules, A with T, C with G.
CRS:
Cambridge reference sequence, referring to the mtDNA of a European
female in Cambridge and used for genetic comparison. The parts of the
mtDNA in the hypervariable region (HVR) which show maximum variation are
called hypervariable sequences 1 and 2 (HVS1, HVS2).
Cytosine: Pyrimidine
base designated as “C” -- one of 4 bases in human DNA.
Diploid: Containing
a complete set of similar chromosomes, one from each parent.
DNA:
Deoxyribonucleic acid. The molecule that encodes genetic
information. A double-stranded helix held together by weak bonds between
base pairs of nucleotides.
DNA bank: Preservation and secure
storage of DNA of known origin for future profiling, diagnostic testing
and research about human physiology, defects and diseases.
DNA
fingerprinting: Refers to identity, paternity, profiling and
forensic analysis of DNA.
DNA probe: Small piece of DNA tagged
with a chemical or radioactive tracers, used to locate a DNA sequence
by hybridization to its complementary sequence.
DNA repair: Carried
out by intracellular proteins which repair damaged DNA.
Double
helix: The structure of DNA, consisting of two strands of
complementary sequences of DNA coiled to form a structure resembling a
spiral staircase.
DYS: Designated Y-chromosome segment. These
markers are valuable in demonstrating genetic association. Unique
identifying numbers are assigned by the Human Gene Nomenclature
Committee (HUGO).
Electrophoresis: Means of identification of
proteins and DNA by migration and separation across an electrical field
in porous material, such as agar, with speed inversely proportional to
weight.
Enzyme: Protein which catalyzes a chemical reaction.
Epigenetic:
Factors other than mutation which modify gene expression.
Eukaryotes:
Organisms having DNA in true nuclei bounded by nuclear membranes.
Exon:
Region of a gene that codes for a protein.
Gene: Sequential
array of DNA nucleotides on a chromosome; the basic unit of heredity.
Genetic
drift: Random change in allelic frequency due to chance, especially
evident in small populations.
Genetics: Study of genes and
their influences on inheritance in a genome and their interactions with
environmental factors.
Genomics: Research and technology
involving all genetic material in the chromosomes of a particular
organism, e.g., 46 chromosomes in humans, containing 3 billion
base-pairs within the nucleus of a cell.
Genotype: Genetic
make-up of a person, as determined by subject’s DNA sequence.
Germ-line
mutation: Abnormality in a germ-line cell which can be transmitted
to subsequent generations.
Guanine: Purine base designated (G)
-- one of 4 base molecules in DNA.
Haplogroup: Large
genetically similar population group found in a recognized geographic
area.
Haplotype: Contraction of “haploid genotype.” Set of
nearby genes or DNA polymorphisms (alleles) inherited as a unit,
containing one of each pair of the 46 human chromosomes. A Y-DNA
haplotype is an arbitrary set of STR markers used to check a genetic
relationship. “Haplotype diversity” refers to the uniqueness of one
haplotype within a defined population.
Hardy-Weinberg law: Mathematical
expression of the equilibrium of allelic genetic markers within a
population.
Heterozygous: Individual having 2 different
alleles of a specific gene.
Homologous: Members of a pair of
chromosomes having similar genes, inherited one from each parent.
Homozygous:
Individual having identical alleles of a given gene.
HVR: Hypervariable
region of mitochondrial DNA used for identification of haplogroups and
genetic mutations (see CRS)
Hybridization: Formation of a
double-stranded DNA molecule between a probe and target DNA.
Indirect
exclusion: A presumed exclusion of parentage based upon the finding
that the child and the alleged father are homozygous for different
alleles. Not considered 100 percent conclusive.
Intron: Region
of a gene that doesn’t code for a protein.
Junk DNA: Much of
the human DNA is non-coding and its medical functions are either
non-existent or limited in scope. Markers found in junk DNA are often
useful for genetic genealogy.
Karyotype: Description of
number and structures of a individual’s chromosomes.
LCR: Ligase
chain reaction, a nucleic amplification method developed by Abbott
Laboratories. Includes tests for Chlamydia (causing trachoma, an eye
disease) and Neisseria (causing gonorrhea). Tests involve probes which
combine with DNA in enlarging cycles to form amplicons (ligated
molecules).
Linkage: Linked genes or markers so closely
located on a chromosome that they are rarely separated by recombination
(significantly less than 50 percent).
Linkage analysis: Statistical
tracking of known genetic markers and diseases in families.
Linkage
disequilibrium: Isolated populations having genealogical evidence
of one or more founders having transmitted a genetic condition, or,
nonrandom association in a population of alleles at nearby loci.
Locus:
A recognized gene site on a chromosome. Genealogists refer to this
as a “marker”.
Marker: In genetic genospeak, a “locus”; a
recognized gene site on a chromosome. Loci are listed as “markers” for
the benefit of genealogists. See also “STR marker.”
Maternal
Match: Determination of probability of the generation of occurrence
of your most recent common ancestor, as demonstrated by mtDNA markers.
MCRA:
Most common recent ancestor shared by two people.
Meiosis: Process
by which a diploid cell goes through 1 round of chromosome replication
and 2 rounds of nuclear division into 4 haploid cells or nuclei, each
having only 1 set of chromosomes.
Mean probability of exclusion: Probability
that a single genetic system with excluse a non-father from paternity
prior to testing.
Messenger RNA (mRNA): DNA is transcribed
into mRNA, which ultimately is translated into a protein.
Microsatellites:
Short sequences of nucleotides (e.g., ATCG) replicated multiple
times in tandem.
Minisatellites: Longer sequences of
nucleotides replicated multiple times in tandem.
Mitochondrial DNA
(mtDNA): DNA found in organelles within a cell’s cytoplasm,
inherited clonally only from mother to all offspring. mtDNA sequences
are used for genealogical studies -- compared with the Standard
Reference Sequence (CSR) for recent events and deep sequences for
occurrences dating several thousand years.
Mitochondrial clock: Concept
of a molecular clock based upon mtDNA mutations occurring at a regular
rate, with very slow rate of nucleotide substitution. The exact rate is
controversial.
Mitoses (human): Nuclear division in humans,
with genetic material divided into 2 chromosomes that have been produced
by fusion of 2 gametes, 1 from the male and 1 from the female parent.
The fusion produces a diploid zygote which then undergoes embryological
development.
MODY: Maturity-onset diabetes of the young --
autosomal dominant diabetes of insulin-deficiency type.
Molecular
biology: Study of DNA, RNA and proteins at the molecular level.
Includes molecular genetics (inheritance) and molecular pathology
(disease processes).
Molecular phylogeny: The inference of
lines of ancestry based upon DNA, RNA or protein sequences obtained in a
laboratory.
Monogenetic: Caused by a single gene mutation.
MRCA:
Most recent common ancestor.
Multiplexing: Using the
polymerase chain reaction (PCR) plus chemicals to amplify markers in DNA
so they are simulatenously copied and tagged.
Mutation: An
abnormal alteration in which DNA affects a genetic coding sequence or
genetic regulatory function. DNA mutations include base substitutions,
transposition, insertions, deletions and exon shuffling.
Mutation
rate: Estimated frequency of genetic mutations. STR markers change
at about 1 mutation/500 transmission events (0.2%), but changes are
random and can occur at any time.
Nucleic acid: Long polymer
structers comprised of nucleotides, such as DNA and RNA.
Nuclease:
Protein which digests nucleic acids or nucleotides, either by
internal or external actions.
Nucleus: Intracellular, confined
portion of a cell, containing genetic material which controls cellular
functions and reproduction.
NASBA: Nucleic acid sequence-based
amplification. DNA amplification method developed by Cangene Corp.,
using 3 enzymes: reverse transcriptase, RHaseH and T7RNA polymerase.
Useful in detection of viruses containing RNA, such as hepatitis C and
HIV.
Nucleotide: Single unit of nucleic acid. In DNA the
building blocks are pyrimidines C and T, purines A and G, plus phosphate
and deoxyribose.
Oligonucleotide: Short string of
nucleotides, used as primers in polymerase chain reactions (PCR).
Oncogene:
Gene capable of causing cancer when mutated.
Paternity index:
Genetic odds in favor of paternity, based upon findings in the
mother, child and alleged father.
PCR: Polymerase chain
reaction -- a biochemical method for in vitro nucleic acid
amplification, producing millions of copies. Carefully selected primers
bind to selected ends to create large amounts of identical DNA for
analysis.
Penetrance: The genetic expression of recognizeable
symptoms. Likelihood that a person carrying a mutation will develop the
characteristics carried by that mutation.
Phenocopy: Phenotype
that mimics genetic influence but is environmentally related.
Phenotype:
Appearance or clinical presentation of one or more genes,
environmental factors, or any combination of these.
Plasmid: Spherical
piece of DNA outside of the chromosome in a bacterium. May replicate
independently from the rest of the bacterial DNA. Commonly used as
cloning vectors to reproduce quantities of a particular DNA.
Polymerase:
Enzyme concerned with production, e.g., DNA or RNA. The 4 varieties
are DDDP, DDRP, RDRP and RDDP (also known as reverse transcriptase).
Polymorphism:
Presence of more than 2 form of a genetic trait.
Population
database: Random sampling of alleles for a given probe used to
determine the frequency of an allele in a population.
Power of
exclusion: Ability of a genetic test to exclude a falsely accused
man of paternity.
Preimplantation genetic testing: One or 2
cells from a live embryo created by in vivo fertilization checked to
rule out genetic disorders.
Primers: Small segments of
double-stranded DNA used to “prime” the site of initiation of DNA
synthesis by DNA-polymerase.
Probability of paternity: Statistical
calculation showing the likelihood that an alleged father is the
biological father of a child.
Proband: Founder or individual
through whom a pedigree is established; male is propositus, female
is proposita.
Probe: Small segment of radioactively
or chemically tagged DNA or RNA used to locate another piece of DNA via
hybridization to its complementary sequence.
Pseudogene: Vestige
of a gene which no longer functions but remains in the genome.
Recessive:
A trait partially or completely masked by a dominant allele.
Recombinant
DNA (rDNA): Shuffling of segments of homologous genes during sex
cell formation, passing on alleles from each parent.
Replication: Process
of making more DNA.
Restriction endonucleases (REs): Restriction
enzymes produced by bacteria (now commercially), capable of cleaving
DNA at specific sites. Used in genetic engineering of diagnostic tests
by creating a recombinant DNA.
Bacteria contain hundreds of enzymes
which recognize and cut over 100 DNA sequences.
Retrovirus: Virus
containing an RNA genome which is converted into a DNA intermediate by reverse
transcriptase enzyme. RNA-containing retroviruses can cause T-cell
leukemia, lymphomas and AIDS.
Reverse transcriptase: An
RNA-dependent DNA polymerase (RDDP) making DNA as directed by an RNA
template. It reverses the flow of genetic information of DNA to RNA to
protein, causing it to go from protein to RNA to DNA.
RFLP: Restriction
enzyme fragment length polymorphism. Variation in the size of DNA
fragments produced by a restriction endonuclease at a polymorphic locus.
RNA:
Ribonucleic acid; intermediary for the flow of genetic information.
A macromolecule composed of small building blocks called nucleotides.
Each nucleotide consists of ribose attached to adenine, guanine,
cytosine and uracil.
Ribosomal RNA (rRNA): A constituent of
the protein-synthesizing machinery of a cell.
Sequencing: Determing
the order of nucleotides (a base sequence) in a DNA or RNA molecule.
Also describes the order of amino acids in a protein.
Sex
chromosomes: Chromosomes which determine sexuality; females have two
X chromosomes, males have one X and one Y chromosome.
Short
tandem repeats: Repeats of short base pairs arranged in tandem.
Single
locus probe: DNA probe that detects a single DNA region.
Somatic
cells: All human body cells except for germ-line sex cells.
Southern
blot: Method of studying DNA sequences developed by Dr. E.
Southern. Variations include dot blot, slot blot.
SNP: Polymorphisms
in which a single nucleotide is altered, e.g., A changed to G.
STR
marker: Short tandem repeat marker. An area of DNA where a small
base sequence showing a base sequence TCTA TCTA TCTA TCTA TCTA TCTA TCTA
TCTA. Genetic markers identified by allelic profiling, used in Y-DNA
testing to identify your haplotype.
Telomeres: Sequences at
the end of chromosomes: TTAAGG
Transmission event: Birth of a
male infant passes on the Y-chromosome to the next generation.
Transcription:
Synthesis of RNA from a DNA template. RNA becomes messenger RNA
(MRNA) and is translated into a protein.
Transfer RNA (tRNA): RNA
molecule transports amino acids to a ribosome for protein systhesis.
Translocation
trisomy: Type of Down syndrome in which material from a chromosome
21 becomes adherent or translocated to another chromosome.
Trisomy:
Presence of an additional chromosome, so there are 3 copies instead
of 2.
VNTR: Variable number of tandem repeats. DNA locations
comprised of short repeats, or 10-70 base pairs arranged in tandem.
X-Chromosome:
Female sex chromosome; females have two X chromosomes; males have
one X, one Y.
YHRD: Database of haplotypes including
predominantly Eurasian samples, but also American, East Asian, Eskimo
Aluet and Amerindian, using up to 11 markers.
X-linked inherited
disease: Single X-chromosome may carry a recessive mutation which
doesn’t become manifest in the mother but can cause X-linked disease,
such as hemophilia or colorblindness, in a male offspring.
Y-chromosome:
Male sex chromosome, transmitted only via the male line.
SELECTED
REFERENCES
Jerger JL: A Medical Miscellany for
Genealogists. Bowie, Md., Heritage Books, 1995
Carmichael T;
Kuklin A: How to DNA Test Our Family Relationships, Moutain View CA,
AceN Press, 2002
Cold
Spring Harbor Laboratory
DNA Heritage
Tutorial
Duerinck K: Genetic Definitions
Farkas, DH: DNA
Simplified: The Hitchhiker’s Guide to DNA. Washington DC, AACP Press,
1996
Guttmacher AE, Collins FS: Genomic Medicine -- A Primer. N
Engl J Med 347, 19 Nov. 7 2002
Russell PJ: Genetics, Ed. 4, New
York NH, HarperCollins, 1996
Genetic terminology can be found in
any standard textbook of genetics. Genetic and genomic glossaries are on
the internet, including http://www.nejm.org