Theory and Problems Genetics

THEORY AND PROBLEMS GENETICS

1- Color blindness in humans is most commonly due to an X-linked recessive allele. Betty has normal vision, but her mother is color blind. Bill is color blind. If Bill and Betty marry and have a child together, what is the probability that the child will be color blind?

2- On average, what proportion of the X-linked genes in the first individual is the same as that in the second individual? (a) A male and his mother (b) A female and her mother (c) A male and his father (d) A female and her father (e) A male and his brother (f) A female and her sister (g) A male and his sister h) A female and her brother)

3- What would the human sexual phenotype (male or female) be? (a) XX (b) XY (c) XO (d) XXY (e) XYY (f) XXYY (g) XXX (h) XXXXX

4- Joe has classic hemophilia, which is an X-linked recessive disease. Could Joe have inherited the gene for this disease from the following persons? Yes No (a) His mother’s mother ______(b) His mother’s father ______(c) His father’s mother ______(d) His father’s father ______

P a g e | 1 5-Both John and Cathy have normal color vision. After 10 years of marriage to John, Cathy gave birth to a color-blind daughter. John filed for divorce, claiming he is not the father of the child. Is John justified in his claim of nonpaternity? Explain why. If Cathy had given birth to a color-blind son, would John be justified in claiming nonpaternity?

6- Red–green color blindness in humans is due to an X-linked recessive gene. A woman whose father is color blind possesses one eye with normal color vision and one eye with color blindness. (a) Propose an explanation for this woman’s vision pattern. (b) Would it be possible for a man to have one eye with normal color vision and one eye with color blindness?

7- Bob has XXY chromosomes (Klinefelter syndrome) and is color blind. His mother and father have normal color vision, but his maternal grandfather is color blind. Assume that Bob’s chromosome abnormality arose from nondisjunction in meiosis. In which parent and in which meiotic division did nondisjunction occur? Explain your answer.

8- The Talmud, an ancient book of Jewish civil and religious laws, states that if a woman bears two sons who die of bleeding after circumcision (removal of the foreskin from the penis), any additional sons that she has should not be circumcised. (The bleeding is most likely due to the X-linked disorder hemophilia.) Furthermore, the Talmud states that the sons of her sisters must not be circumcised, whereas the sons of her brothers should. Is this religious law consistent with sound genetic principles? Explain your answer.

P a g e | 2 9- How many Barr bodies would you expect to see in human cells containing the following chromosomes? (a) XX (d) XXY (g) XYY (b) XY (e) XXYY (h) XXX (c) XO (f) XXXY (i) XXXX

10- Red–green color blindness is an X-linked recessive trait in humans. Polydactyly (extra fingers and toes) is an autosomal dominant trait. Martha has normal fingers and toes and normal color vision. Her mother is normal in all respects, but her father is color blind and polydactylous. Bill is color blind and polydactylous. His mother has normal color vision and normal fingers and toes. If Bill and Martha marry, what types and proportions of children can they produce?

11- A color-blind female and a male with normal vision have three sons and six daughters. All the sons are color blind. Five of the daughters have normal vision, but one of them is color blind. The color-blind daughter is 16 years old, is short for her age, and has never undergone puberty. Propose an explanation for how this girl inherited her color blindness.

P a g e | 3 12- A man with a specific unusual genetic trait marries an unaffected woman and they have four children. Pedigrees of this family are shown in parts a through e, but the presence or absence of the trait in the children is not indicated. For each type of inheritance, indicate how many children of each sex are expected to express the trait by filling in the appropriate circles and squares. Assume that the trait is rare and fully penetrant.

P a g e | 4 For each of the following pedigrees, give the most likely mode of inheritance, assuming that the trait is rare. Carefully explain your reasoning.

P a g e | 5 R & X

P a g e | 6 The following pedigree represents the inheritance of a rare disorder in an extended family. What is the most likely mode of inheritance for this disease? (Assume that the trait is fully penetrant.)

Classic hemophilia is inherited as an X-linked recessive trait. This pedigree is of hemophilia in the royal families of Europe

P a g e | 7 The Study of Human Genetic Characteristics

Humans are the best and the worst of all organisms for genetic study. On the one hand, we know more about human anatomy, physiology, and biochemistry than we know about most other organisms; for many families, we have detailed records extending back many generations; and the medical implications of genetic knowledge of humans provide tremendous incentive for genetic studies. On the other hand, the study of human genetic characteristics presents some major obstacles.

First, controlled matings are not possible. With other organisms, geneticists carry out specific crosses to test their hypotheses about inheritance. We have seen, for example, how the testcross provides a convenient way to determine if an individual with a dominant trait is homozygous or heterozygous. Unfortunately (for the geneticist at least), matings between humans are more frequently determined by romance, family expectations, and—occasionally—accident than they are by the requirements of the geneticist. Another obstacle is that humans have a long generation time. Human reproductive age is not normally reached until 10 to 14 years after birth, and most humans do not reproduce until they are 18 years of age or older; thus, generation time in humans is usually about 20 years. This long generation time means that, even if geneticists could control human crosses, they would have to wait on average 40 years just to observe the F2 progeny. In contrast, generation time in Drosophila is 2 weeks; in bacteria, it’s a mere 20 minutes. Finally, human family size is generally small. Observation of even the simple genetic ratios that we learned in Chapter 3 would require a substantial number of progeny in each family. When parents produce only 2 children, it’s impossible to detect a 3:1 ratio. Even an extremely large family with 10 to 15 children would not permit the recognition of a dihybrid 9:3:3:1 ratio. Although these special constraints make genetic studies of humans more complex, understanding human heredity is tremendously important. So geneticists have been forced to develop techniques that are uniquely suited to human biology and culture.

Concepts Although the principles of heredity are the same in humans and other organisms, the study of human inheritance is constrained by 1) the inability to control genetic crosses, 2) the long generation time, and 3) the small number of offspring.

P a g e | 8 Analyzing Pedigrees

An important technique used by geneticists to study human inheritance is the pedigree. A pedigree is a pictorial representation of a family history, essentially a family tree that outlines the inheritance of one or more characteristics.

Standard symbols are used in pedigrees.

P a g e | 9 P a g e | 10 I- Autosomal a) Recessive Traits

Concepts 1. Autosomal recessive traits appear with equal frequency in males and females. 2. Affected children are commonly born to unaffected parents, and the trait tends to skip generations. 3. Recessive traits appear more frequently among the offspring of consanguine matings.

P a g e | 11 I- Autosomal b) Dominant Traits

Concepts

1. Autosomal dominant traits appear in both sexes with equal frequency. 2. Affected persons have an affected parent (unless they carry new mutations), and 3. The trait does not skip generations. 4. Unaffected persons do not transmit the trait.

P a g e | 12 II- X-Linked a) Recessive Traits

Concepts

1. Rare X-linked recessive traits appear more often in males than in females and 2. Are not passed from father to son. 3. Affected sons are usually born to unaffected mothers; 4. Thus X-linked recessive traits tend to skip generations.

P a g e | 13 II- X-Linked b)Dominant Traits

Concepts 1. X-linked dominant traits affect both males and females. 2. Affected males must have affected mothers (unless they possess a new mutation), and 3. They pass the trait on to all their daughters.

P a g e | 14 III- Y-Linked Traits

Concepts 1. Y-linked traits appear only in males and 2. Are passed from a father to all his sons.

P a g e | 15 Supplemental Lecture (97/06/10 update) by Stephen T. Abedon ([email protected])

1. Chapter title: Pedigree Analysis Problems a. A list of vocabulary words is found toward the end of this document 2. Vocabulary a. No entry. 3. Practice questions - The below questions are from pp. 60, 68-70 of Sinnott et al. , 1958: a. Which best describes the genetics of the afflicting allele in the following pedigree (it is a pedigree of taste blindness)? [PEEK] i. autosomal dominant ii. autosomal recessive iii. X-linked dominant

P a g e | 16 iv. X-linked recessive v. Y-linked dominant vi. Y-linked recessive

b. Albinism is inherited as an autosomal recessive. In the figure below, assuming that persons from the general population are not heterozygous for albinism (Aa), what are the genotypes of all persons whose genotypes are known? (i.e., indicate the genotypes on the figure for all known AA, Aa, and aaindividuals) [PEEK]

P a g e | 17 c. A blue-eyed man marries a brown-eyed woman. They have one child, who is blue eyed. What are the genotypes of all the individuals mentioned?[PEEK] d. Given the below pedigree, would you expect to find more of in Cleopatra-Berenike III compared with the general population? (figure from p. 283 of R. Lewis, 1998, Life Third Edition. McGraw Hill, Boston, Mass.). [PEEK] i. Loci which are heterozygous ii. Loci which are homozygous for rare alleles iii. Loci which display epistasis iv. Loci which display codominance v. Alleles vi. Loci

e. Suppose that an allele, b, of a sex-linked gene is recessive and lethal. A man marries a woman who is heterozygous for this gene. If this couple had a large number of normal children, what would be the predicted sex

P a g e | 18 ratio of these children (ratio of male children to female children)? (adapted from J.L. Gould and W.T. Keeton (1996). Biological Science. Sixth Edition. W.W. Norton & Company. New York. P. 443) [PEEK] f. In Drosophila melanogaster there is a dominant allele for gray body color and a dominant allele of another gene for normal wings. The recessive alleles of these two genes result in black body color and vestigial wings, respectively. Flies homozygous for gray body and normal wings are crossed with flies that have black bodies and vestigial

wings. The F1 progeny are then crossed, with the following results: g. Gray body, normal wings: 236 h. Black body, vestigial wings: 253 i. Gray body, vestigial wings: 50 j. Black body, normal wings: 61 k. Would you say that these two genes are linked? If so, how many map units apart are they on the linkage map? (adapted from J.L. Gould and W.T. Keeton (1996). Biological Science. Sixth Edition. W.W. Norton & Company. New York. P. 443) [PEEK] l. An afflicted woman marries an afflicted man. The allele causing the affliction is recessive to the wild type allele. What fraction of their children will be silent carriers? What fraction will be afflicted? [PEEK] m. For the following pedigree, how does the afflicting allele impact on phenotype? (figure is from M.R Cummings (1988). Human Heredity: Principles and Issues West Publishing Company. New York. p. 113) [PEEK] i. it displays complete dominance ii. it is recessive to the non-afflicting allele otherwise found at the same loci iii. it displays epistasis iv. it displays pleiotropic effects v. it produces a tRNA product vi. it is a Mendelian ratio

P a g e | 19 n. If a husband and wife have four daughters. Under most circumstances, what is the probability that their fifth child will also be a girl? (adapted from G.T. Licata & W.H. Garnsey (1986). A General Review of Biology 2nd Edition. N & N Publishing, Middletown, NY, p. 119 [PEEK] o. A male cat has short hair, a stubby tail, and extra toes. A female cat has long hair, a long tail, and extra toes. The genes and alleles are as follows: p. L = short hair; l = long hair q. M = stubby tail; m = long tail r. P = extra toes; p = normal number of toes s. The two cats have kittens. One kitten has long hair, a long tail, and no extra toes. Another has short hair, a stubby tail, and extra toes. The third kitten has short hair, a long tail, and no extra toes. What is the genotype of the father. (adapted from R. Lewis (1998). Life Third Edition. McGraw-Hill, Boston, Mass., p. 283)[PEEK] t. The recombination frequency between linked genes A and B is 40%, between B and C is 20%, between C and D is 10%, between C and A is 20%, and between D and B is 10%. What is the sequence of the genes on the chromosome? (adapted from J.L. Gould and W.T. Keeton (1996). Biological Science. Sixth Edition. W.W. Norton & Company. New York. P. 443)[PEEK] 4. Practice question answers a. ii, autosomal recessive. b. in the figure below, all individuals from the general population (i.e., married in spouses) are AA. All circled individuals are Aa. All afflicted individuals areaa.

P a g e | 20 c. if b is the recessive blue-eyed allele and B the dominant brown-eyed allele, then the man is bb, the woman Bb, and the child bb. d. ii, Loci which are homozygous for rare alleles e. 1:2 (i.e., half the male children would die) f. (50 +61) / (236 + 253 + 50 +61) = 18.5, so yes and 18.5 map units apart g. All will be afflicted and none will be silent carriers. h. i, it displays complete dominance. i. 0.5 j. Ll Mm Pp k. A-C-D-B 5. References a. Sinnott, E.W., Dunn, L.C., Dobzhansky, T. (1958). Principles of Genetics. Fifth Edition. McGraw-Hill Book Co., Inc. New York. p. 60, 68-70.

Genetics Vocabulary

1. Allele — alternative forms of a gene for each variation of a trait of an organism

P a g e | 21 2. Crossing over — exchange of genetic material between non-sister chromatids from homologous chromosome during prophase I of meiosis; results in new allele combinations 3. Diploid — cell with two of each kind of chromosome; is said to contain a diploid, or 2n, number of chromosomes 4. Dominant — observed trait of an organism that mask the recessive form of a trait 5. Egg — haploid female sex cell produced by meiosis 6. Fertilization — fusion of male and female gametes 7. Gamete — male and female sex cells, sperm and eggs 8. Genetic recombination — major source of genetic variation among organisms caused by re-assortment or crossing over during meiosis 9. Genetics — branch of biology that studies heredity 10. Genotype — combination of genes in an organism 11. Haploid — cell with one of each kind of chromosome; is said to contain a haploid or n, number of chromosomes. 12. Heredity — passing on of characteristics from parents to offspring 13. Heterozygous — when there are two different alleles for a trait 14. Homologous chromosome — paired chromosomes with genes fro the same traits arranged in the same order. 15. Homozygous — when there are two identical alleles for a trait 16. Hybrid — offspring formed by parents having different forms of a specific trait. 17. Law of independent assortment — Mendelian principal stating that genes for different traits are inherited independently of each other. 18. Law of segregation — Mendelian principal explaining that because each plant has two different alleles, it can produce two different types of gametes. During fertilization, male and female gametes randomly pair to produce four combinations of alleles 19. Meiosis — type of cell division where one body cell produces for gametes, each containing half the number of chromosomes in a parent’s body. 20. Nondisjunction — failure of homologous chromosomes to separate properly during meiosis; results in gametes with too many or too few chromosomes 21. Phenotype — outward appearance of an organism, regardless of its genes. 22. Pollination — transfer of male pollen grains to the pistil of a flower 23. Recessive — trait of an organism that can be masked by the dominant form of a trait

P a g e | 22 24. Sexual reproduction — pattern of reproduction that involves the production of subsequent fusion of haploid cells. 25. Sperm — haploid male sex cells produced by meiosis 26. Trait — characteristic that is inherited; can be either dominant or recessive 27. Zygote — diploid cell formed when a sperm fertilizes an egg.

Terms to know in Mendelian Genetics alleles The different forms of a gene. Y and y are different alleles of the gene that determines seed color. Alleles occupy the same locus, or position, on chromosomes. autosomal A locus on any chromosome but a sex chromosome. Not sex-linked. co-dominant alleles Two different alleles at a locus are responsible for different phenotypes, and both alleles affect the phenotype of the heterozygote. For example, consider the situation where there are three alleles A,B, and O that determine human blood type. Three possible genotypes are AA, BB, OO that correspond to the phenotypes of blood type A, B, and O respectively; Two other genotypes are AO and BO that correspond to blood types A and B, respectively because the O allele is recessive, The remaining genotype is AB, corresponding to blood type AB. Both the A and B alleles contribute to the phenotype of the heterozygote. Thus the alleles A and B are said to be co-dominant. complete linkage. Complete linkage describes the inheritance patterns for 2 genes on the same chromosome when the observed frequency for crossover between the loci is zero. dioecious Organisms produce only one type of gamete; i.e. humans dominant trait. A trait expressed preferentially over another trait. Drosophila melanogaster The fruit fly, a favorite organism for genetic analysis. epistasis. One gene masks the expression of a different gene for a different trait. F1 generation

P a g e | 23 Offspring of a cross between true breeding plants, homozygous for the trait of interest F2 generation Offspring of a cross involving the F1 generation. genotype The genetic constitution of an organism with respect to a trait. For a single trait on an autosome, an individual can be homozygous for the dominant trait, heterozygous, or homozygous for the recessive trait. Yellow seeds are dominant, but yellow seeded plants could have a genotype of either YY or Yy. hemizygous If there is only one copy of a gene for a particular trait In a diploid organism, the organism is hemizygous for the trait, and will display a recessive phenotype. X-linked genes in fly or human males are hemizygous. heterozygous Differing alleles for a trait in an individual, such as Yy. homologous chromosomes The pair of chromosomes in a diploid individual that have the same overall genetic content. One member of each homologous pair of chromosomes in inherited from each parent. homozygous Both alleles for a trait are the same in an individual. They can be homozygous dominant (YY), or homozygous recessive (yy). hybrid heterozygous; usually referring to the offspring of two true-breeding (homozygous) individuals differing in the traits of interest. incomplete dominance Intermediate phenotype in F1, parental phenotypes reappear in F2. The flowers of the snapdragon plant can be red, pink, or white. Color is determined at a single locus. The genotype RR results in red flowers and rr results in white flowers. The heterozygote genotype of Rr results in pink flowers. When the heterozygote has a different, intermediate phenotype compared to the homozygous dominant or homozygous recessive individuals, this is said to be incomplete dominance. lethal alleles. Mutated genes that are capable of causing death. linkage. genes that are inherited together on the same chromosome. Three inheritance patterns are possible: non-linkage, Partial linkage, and complete linkage. mendel's law of independent assortment of alleles. Alleles of different genes are assorted independently of one another during the formation of gametes.

P a g e | 24 mendel's law of segregation Alleles segregate from one another during the formation of gametes. monoecious Organisms produce both male and female gametes; i.e. garden pea. monohybrid cross. Cross involving parents differing in only one trait. mutation Change in the DNA sequence of a gene to some new, heritable form. Generally, but now always a recessive allele. non-linkage. Non-linkage describes the inheritance patterns for 2 genes on the same chromosome, when the expected frequency for crossover between the loci is at least one. The observed inheritance patters for non-linked genes on the same chromosome is the same as for 2 genes on different chromosomes. partial linkage. Partial linkage describes one of the inheritance patterns for 2 genes on the same chromosome, when the expected frequency for crossover between the loci is greater than zero but less than one. From partial linkage analysis we can learn about the order and spacing of genes on the same chromosome. phenotype The physical appearance of an organism with respect to a trait, i.e. yellow (Y) or green (y) seeds in garden peas. The dominant trait is normally represented with a capital letter, and the recessive trait with the same lower case letter. pleiotropic. A single gene determines more than one phenotype for an organism. recessive trait. The opposite of dominant. A trait that is preferentially masked. reciprocal cross Using male and female gametes for two different traits, alternating the source of gametes. sex chromosomes Sex determination is based on sex chromosomes sex-linked. A gene coded on a sex chromosome, such as the X-chromosome linked genes of flies and man. test cross Generally a cross involving a homozygous recessive individual. When a single trait is being studies, a test cross is a cross between an individual with the dominant phenotype but of unknown genotype (homozygous or heterozygous) with a homozygous recessive individual. If the unknown is heterozygous, then approximately 50% of the offspring should display the recessive phenotype.

P a g e | 25 true-breeding Homozygous for the true-breeding trait. wild-type allele The non-mutant form of a gene, encoding the normal genetic function. Generally, but not always a dominant allele.

The Biology Project University of Arizona Tuesday, August 13, 1996 [email protected]

Acceptor site - see splice acceptor site

Acentric fragment A piece of chromosome without a centromere

3' UTR, 3' Untranslated Region The part of the mRNA which lies between the signal for the termination of translation (the stop codon) and the polyA tail.

5' UTR, 5' Untranslated Region The part of the mRNA which comes before the AUG codon which initiates translation.

Acrocentric A chromosome with its centromere very close to (but not actually at) one end. It applies to human chromosomes 13, 14, 15, 21 and 22.

Allele One of alternative forms of a gene at a particular locus.

Alu repeat sequence A member of a family of repeated DNA sequence elements which is particularly abundant in the primates (about 3 × 105 copies in the human genome). Alus are approximately 300 base pairs long, often contain a site for the restriction endonuclease Alu I and have been derived from a small number of active members via transcription and retroposition (which still continues). The insertion of an alu element can cause mutation.

Amino Acid One of the building blocks of proteins. See your textbooks!

P a g e | 26 Amniocentesis A procedure used in antenatal diagnosis of genetic abnormality in which a sample of the amniotic fluid surrounding the foetus is removed, and either DNA is prepared directly from the amniocytes suspended in it or these cells may be cultured and their chromosomes examined.

Amniocyte A foetal cell found suspended within the amniotic fluid surrounding the foetus.

Amplification

 As in PCR Amplification - exponential increase of the number of copies of a specific DNA sequence in vitro by using the polymerase chain reaction.  As in various types of gene mutation such as trinucleotide repeat amplification or myc gene amplification - naturally occuring aberrations which have greatly increased the copy number of a triplet repeat or of a whole gene respectively in vivo.  As in amplified library, a clone library which has undergone at least one round of colony or plaque formation followed by resuspension.

Anaphase The stage in a cell division at which the chromosomes move to opposite ends of the spindle

Aneuploid A set of chromosomes which does not contain an exact multiple of haploid sets of chromosomes.

Anticipation The process whereby some genetic diseases get more severe in each successive generation.

Antisense strand (of DNA) The DNA strand which carries the complementary sequence to the mRNA. It is of course the strand which is actually transcribed into the mRNA.

Archaebacteria A phylum of organisims distinct from both prokaryotes and eukaryotes.

Ascertainment The method by which individuals (and families) come to attention for genetic study.

Assortative mating The tendency for mates to be chosen non randomly. Mates may be chosen for a shared characteristic (positive assortative mating) or chosen to be different (negative ditto)

P a g e | 27 Assortment The movement of homologous chromosomes to opposite poles in the first meiotic division (and chromatids in the second meiotic division) leading to the segregation of alleles. It is (usually) random with respect to each chromosome.

Autosome A chromosome which is not a sex chromosome.

Autoradiography A technique which reveals the position of radioactive isotope (such as 35S, 32P or 33P) within an experimental result. The experiment containing a radioactive label is held tightly against a piece of unexposed X-ray film in the dark. After an appropriate period the X-ray film is developed and the positions on the film which have been exposed to radiation from the isotope are revealed.

Bacteriophage A virus which infects bacteria. Modified bacteriophages are used as cloning vectors. Two which are commonly encountered are bacteriophage lambda and bacteriophage M13.

Banding A reproducible pattern of light and dark staining along the length of a chromosome.

Barr body An X chromosome which is condensed and inactive and which shows as a dark staining blob in an interphase nucleus.

Base A (chemically) basic part of a nucleic acid. Adenine (A), thymine (T), cytosine (C), guanine (G) and uracil (U). See base pair, nucleoside and nucleotide.

Base pair (bp) The fundamental unit of a double stranded DNA molecule, (more strictly - a nucleotide pair). The base Adenine on one strand is paired with Thymine on the other and Guanine with Cytosine. The lengths of double stranded DNA molecules are frequently given in bp (or nucleotide pairs).

Bivalent A pair of homologous chromosomes closely associated in prophase and metaphase of the first meiotic division.

Blot To transfer DNA, RNA or Protein from an electrophoresis medium (such as agarose or polyacrylamide) to a support (such as a nylon membrane) where it becomes accessible for analysis (by hybridisation to a nucleic acid probe, or by binding a specific antibody). See Southern, Northern and Western blots.

Candidate gene A gene which by virtue of either its function or of its map position might be considered as the possible cause of a genetic disease when mutant.

Carrier A person heterozygous for a recessive trait.

P a g e | 28 cDNA - Complementary DNA - DNA which has at some point in its history been made by copying RNA using the enzyme reverse transcriptase. See theTechniques lecture

CentiMorgan (cM) The unit of distance in genetic maps. Over short distances, if two genes are 1 cM apart then they will recombine on average 1% of the time.

Centromere The point at which a chromosome attaches to the spindle fibres during cell division. Visible as a constriction in the thickness of a metaphasechromosome.

Chain termination mutation A mutation which leads to the premature termination of the polypeptide chain specified by the mutant gene. Nonsense mutations,frameshift mutations and splice junction mutations can all give rise to premature chain termination.

Chiasma (plural chiasmata) Literally a cross. The point at which a genetic recombination event has occurred, visible as a cross-over in meiotic prophase.

Chimaera (chimera) An animal (or plant) made up from a mixture of cells from more than one species. Also (in human genetics), an individual made up from cells derived from two or more zygotes.

Chorionic villus sampling (CVS) A technique used in antenatal diagnosis where a small amount of placental tissue is removed at about 8 - 9 weeks of gestation by transcervical aspiration. Foetal DNA or chromosomes can then be prepared from the tissue. See also amniocentesis

Chromatid A chromosome at metaphase can be seen to be made up of two identical sister chromatids held together at the centromere. At anaphase one chromatid will go to each pole.

Chromatin The complex of DNA in the nucleus with histone and non-histone proteins.

Chromosome The structure which is built up around each nuclear DNA molecule. It is comprised of a single (double stranded) DNA molecule with associatedhistone proteins, non-histone proteins and RNA. It is most easily viewed at its most condensed (at metaphase of mitosis) when its structure has been duplicated to give two chromatids. All normal human chromosomes have a centromere, two arms and two telomeres.

P a g e | 29 Chromosome jumping A (difficult?) cloning method which can be used to isolate clones at a desired distance (in the range of 100 - 300 kb) along a chromosome from the starting clone.

Chromosome walking A method of making a detailed map of a chromosome by isolating successive overlapping clones. Usually each clone is used as a probe to isolate the next.

 noun Is frequently used to mean a DNA molecule which has been replicated in a micro-organism such as a bacterium or yeast to make many thousands or millions of identical molecules. It also means an individual who is genetically identical to another individual. This might mean an identical twin but it is often used to mean a cell line in which each cell is identical to all the others because they are all derived by cell division from a common ancestor.  Verb to carry out the process of replicating an individual or a specific DNA molecule.

Coding strand Within a gene, this is the DNA strand which has the same sequence of bases as the primary transcript (with the substitution of T for U obviously). It is also called the sense strand.

Coding sequence That part of a gene which contains the codons which will, via a mRNA intermediate, be translated into polypeptide. Its antithesis is non-coding sequence.

Codominant Used to describe alleles which can both be recognised in the phenotype of a compound heterozygote.

Codon A group of three consecutive nucleotides in mRNA which specifies an amino acid to be incorporated in the polypeptide product of the gene. See genetic code.

Coefficient of inbreeding The proportion of the genes of an individual in which both copies are identical by descent from a common ancestor. Alternatively, the chance that both alleles of any one gene are identical by descent.

ColonyThe small heap of bacteria which are the descendents of a single bacterium placed on a nutrient agar dish and allowed to incubate for some hours (usually overnight).

P a g e | 30 Colony Screen. Bacterial colonies are grown on a nylon filter placed on nutrient agar. The colonies are lysed in situ in conditions similar to those of a Southern blotso that the DNA which each contains adhers to the filter at the site of each colony and is available for hybrisation to a specific probe. In this way a clone which contains the probe sequence may be identified.

Complementary (As in complementary strand) having the sequence of nucleotides which will form a base paired double helix with another strand of DNA or RNA.

Complementary DNA see cDNA

Complementation The ability of two different mutations to produce a wild type phenotype in a double heterozygote. This gives a very strong indication that they do not both affect the same gene (cases of intragenic complementation are very rare).

Compound heterozygote An individual in whom both alleles at a single locus carry a different mutation.

Complexity In molecular genetics, used to describe a DNA molecule or a mixture of DNA molecules. It is the length of the sequence without including any sequence repetition.

Congenital Present at birth but not necessarily inherited.

Consanguineous mating A mating in which male and female are related by descent.

Contiguous gene syndrome A syndrome caused by a deletion which has removed one copy of a number of genes which are close together in the genome.

Cosmid A type of cloning vector which is based on a plasmid but which contains one copy (or sometimes two copies) of the lambda cohesive end. This enables recombinant molecules to be packaged into lambda phage particles which are able to infect recipient bacteria. It is thus a very efficient way of creating libraries of relatively high molecular weight genomic DNA. The average insert size in a cosmid is 40 - 45 kb.

C0t 1 DNA Eukaryotic DNA which has been denatured and allowed to reanneal to a

C0t value of 1. The double stranded component is then purified from the single stranded component and is supplied commercially. It contains most of the repetitive component of the genome but very little single copy DNA.

P a g e | 31 CpG means the dinucleotide: Cytidine joined by a 5´ to 3´ phospho-diester linkage to Guanidine as part of a normal DNA strand.

Crossover The reciprocal exchange of genetic material between homologous chromosomes in meiosis. A point along the length of a meiotic bivalent where the homologous chromosomes can be seen to have exchanged chromatids. See chiasma and genetic recombination.

Cryptic splice site A DNA sequence which is similar to the consensus sequence of a splice site but which is not normally used. It may be activated if a mutationalters or removes a genuine nearby site. It may be in coding or non-coding DNA sequence.

Cytogenetic location The region (or point) in the cytogenetic banding pattern within (or at) which a gene (or cloned DNA fragment etc.) is thought to lie. A cytogenetic map is comprised of many such pieces of information.

Deletion A mutation resulting in the loss of normal DNA sequence. A deletion may be of any size from 1 nucleotide pair to the loss of most of a chromosome.

Denaturation - of DNA - conversion from double stranded to single stranded form, often by heating sometimes by treatment with alkali. - of protein - treatment which destroys the tertiary structure of a protein.

Deoxyribonucleic acid see DNA

Depth as in "depth of library". The average number of times any sequence, originally present in a single copy in the genome, will be represented in a genomic library. A typical library will have a depth of from 3 to 10.

Dicentric a structurally abnormal chromosome with two centromeres

Diploid having two haploid sets of chromosomes

Dizygotic twins twins arising by the fertilisation of two eggs by two sperm. therefore no more identical than normal sibs.

DNA The molecule in which the genetic information of most organisms is encoded. See textbooks and first year lecture notes for more detail!

DNA fingerprinting A process by which an individual can be uniquely identified (well, narrowed down substantially!) by testing for multiple DNA polymorphisms.

P a g e | 32 Often, for forensic purposes, the source of the DNA may be only a tiny spot of blood or a hair root etc. See here for a diagram

DNA methylation in vertebrates The addition of a methyl group to a cytosine base of a CpG dinucleotide to form 5-methylcytosine. in micro-organisms many other methylation positions may be used.

DNA polymerase an enzyme which makes DNA from nucleotide triphosphates. Usually it requires a single stranded template (either DNA or RNA) and a short primer (again either DNA or RNA) to enable it to make a complementary copy.

Dominant An allele is dominant if its effect can be observed in the phenotype of a heterozygote.

Dominant negative mutation The mutant polypeptide disrupts the function of the wild type polypeptide in heterozygotes.

Donor site see splice donor site.

Dosage compensation The imbalance caused by having two copies of the X chromosome in females compared to only one copy in males is countered (in humans) by X inactivation or (in Drosophila) by reducing the relative level of activity of X linked genes in females.

Downstream Genes have an orientation which is defined by their direction of transcription (5' to 3'). Downstream means further in the direction of transcription of a gene and even possibly beyond its end.(Opposite is upstream.)

Electrophoresis A technique whereby molecules are separated by movement in an electric field. In zone electrophoresis the molecules are ordered on the basis of their charge to weight ratios. In agarose and polyacrylamide gel electrophoresis the matrix plays a significant role in sieving the molecules which are therefore separated much more on the basis of their sizes.

Enhancer A DNA sequence, usually, but not necessarily, near the promoter, which will increase the level of transcription of genes attached to it on the same DNA molecule. Its effect is independent of orientation and though it is usually within 5 kb of a gene, it may be able to work over distances as great as 50 kb. It may beupstream or downstream of the gene.

Epigenetic any factor which influences the phenotype which is not part of the genotype.

P a g e | 33 EST, Expressed sequence tag An (usually) incompletely sequenced cDNA. Knowledge of sequence allows the design of a PCR reaction which may be used to test for its presence. Most ESTs have been generated from the 3' UTRs of genes.

Euchromatin noun (and Euchromatic adjective) chromatin with a normal pattern of replication and gene expression. Compare with heterochromatin.

Eukaryote A class of organisms (which may be single or multicellular) in which the genetic material is contained within a nucleus. There are other specialised structures too which are unique to eukaryotes. See prokaryotes and archaebacteria.

Euploid A genome which contains a whole number of haploid sets of chromosomes. See aneuploid.

Exon One of the parts of a gene whose sequence is present in the mature mRNA.

Expressivity The degree of expression of a mutant phenotype. If there is a variable expressivity it may range from mild symptoms to a severe phenotype. See alsopenetrance.

Familial trait A trait which is more common in the relatives of an affected person.

Fitness A measure of an organism’s or a genotype’s ability to leave offspring in the next generation. It is the number of offspring left by that individual (or the average left by individuals of a particular genotype) divided by the average number of offspring left by all members of the population.

Flanking sequence The DNA on either side of a gene. See upstream and downstream.

Founder effect A high frequency of a particular allele in a population caused by it having been present in one or more members of a small number of individuals from whom the population is descended.

Frameshift mutation A mutation which, by deletion or addition of a number of basepairs which is not divisible by three, causes an alteration in the reading frame of a gene.

G bands The pattern of dark and light coloured Giemsa stained bands on metaphase chromosomes. See Giemsa banding

P a g e | 34 g force The force exerted on an object due to gravity. The centrifugal force exerted by a centrifuge is often given in units of G. Where G = the force exerted on a 1kg mass at the Earth's surface.

Gamete A sperm or an ovum.

Gene In Mendelian terms - a unit of inheritance. In molecular terms - a region of DNA which contains the information to create either a functional RNA or a polypeptide chain.

Gene dosage The number of copies of a gene which are present in the genome.

Gene family A number of genes which resemble each other in DNA sequence, presumably because they have evolved by gene duplication and subsequent divergence.

Gene flow The movement of alleles from one population into another.

Gene map A diagram of the relative positions of genes within the genome

Gene pool All the alleles at a particular locus present in a population.

Genetic code The rules for converting the sequence of nucleotides in mRNA into a sequence of amino acids in a polypeptide.

Genetic disease A disorder, which may or may not be apparent at birth, which is a consequence of a mutation present in one or more of the patient's genes.

Genetic Drift Random changes in allele frequencies from one generation to another in finite (small) populations

Genetic heterogeneity Similar phenotypes caused by mutations in more than one gene.

Genetic map A map showing the distances between markers in terms of the frequency of genetic recombination between them.

Genetic marker A polymorphic locus which can be used in linkage studies. The polymorphism may be anything to do with the DNA at the locus or its possible product so long as it can be recognised with an appropriate test. Examples include polymorphisms such as a single nucleotide change, an RFLP,

P a g e | 35 a microsatellitepolymorphism, an electrophoretic variant of a protein, a blood group, a genetic disease etc.

Genome The complete DNA sequence of an organism (though it may sometimes be used in the sense of ‘mitochondrial genome’ or ‘nuclear genome’).

Genomic DNA DNA derived from the genome, as distinct to cDNA. It may have been directly purified but it may also have been manipulated in some way, byPCR for instance or by cloning.

Genotype The alleles present in an individual at the locus (loci) under consideration. Alternatively, the sum of all the alleles present in a genome.

Germline The cells which are in direct mitotic line of descent from the zygote to its gametes. As distinct from somatic cells.

Germline mosaicism Two populations of cells making up the germline of one individual. Caused by mutation and proliferation of one cell out of the population of germline cells.

Giemsa banding A way of treating metaphase chromosomes with trypsin and Giemsa stain to give a reproducible pattern of dark and light coloured bands.

Haploid In the human case, having exactly one copy of each of the autosomes and one sex chromosome. (In the case of an organism with a non-chromosomal method of sex determination then having just one copy of the genome.)

Haplotype A set of closely linked alleles which are inherited together.

Hardy-Weinberg law A rule which relates the frequencies of genotypes at a locus in a population to the frequencies of the alleles at that locus.

Hemizygous Having only one copy of a chromosome rather than the usual two. Used most often in describing the X chromosome in males but can be used to describe any chromosome or (in the case of a deletion) any segment of chromosome.

Heritability The extent to which a trait is genetically determined.

Heterochromatin Chromatin which is condensed in interphase and which replicates later than the rest of the genome. Can be subdivided into facultativeheterochromatin (which describes the inactivated X chromosome, inactivated randomly in only half the cells of a female) and constitutive heterochromatin which contains a high content

P a g e | 36 of tandemly repeated (satellite) DNA sequences and relatively few genes and which is always heterochromatic.

Heterokaryon A cell with more than one nucleus formed by the fusion of two or more cells (usually of different species). The first stage in making a somatic cell hybrid.

Heteromorphism Normal variation in the shape or staining of a chromosome. It may often involve variation in the amount of heterochromatin.

Heterozygote (adj. heterozygous) An individual having two different alleles at a locus.

Histones Very basic proteins which bind tightly to the acidic DNA to form a nucleosome - the basic building block of chromatin. They are highly conserved throughout eukaryotic evolution.

Homologous chromosomes A pair of chromosomes containing essentially the same genetic information which have been inherited one from each parent.

Homozygote (adj. homozygous) An individual having two identical alleles at a locus.

Housekeeping gene A gene which is expressed at a similar level in almost all cells, presumably because its product is required for cell viability.

Hybrid An organism made by crossing two different species. (Or, of a cell line, a cell line made by fusing cells of two different species; or of a DNA duplex, having one strand from one source and one from another.)

Hybridisation Used in molecular biology to describe the process of annealing one strand of a polynucleotide (DNA or RNA), the probe, to a strand ofcomplementary sequence (again either DNA or RNA), the target. Also, the process of forming a hybrid. Used in many techniques such as Southern and NorthernBlotting, in situ Hybridisation, colony screening.

Imprinting The differential expression of genes depending on whether they were inherited maternally or paternally.

Inborn error of metabolism A mutation which results in the absence of an enzyme leading to a metabolic consequence which may be fatal.

Inbreeding The mating of related individuals.

P a g e | 37 Insertion mutation A mutation caused by the addition of genetic material into a gene.

In situ hybridisation Hybridisation of a labelled probe to its target which has been fixed for visualisation by microscopy. It is used to reveal the position of sequences corresponding to the probe on metaphase chromosomes, in interphase nuclei, on stretched DNA molecules and also to reveal the cellular location of RNAtranscripts corresponding to the probe sequence.

Interphase That portion of the cell cycle when the nuclear membranes have formed, the chromosomes have decondensed and the cell is going about its normal business. During this interval DNA replication takes place.

Interspersed repetitive DNA DNA sequences which are present many thousands of times in each haploid genome, which are widely scattered throughout the genome and which are not particularly concentrated at any point. Examples include Alu and Line sequences.

Intervening sequence See intron

Intron A part of the gene which is transcribed but which is removed (by the process of splicing) from the primary transcript in the formation of mRNA. Intronstherefore remain in the nucleus.

Inversion A chromosomal rearrangement in which a segment of chromosome is turned end for end. A pericentric inversion includes the centromere, a paracentric inversion does not.

Isochromosome A chromosome in which one arm has been lost and has been replaced by a duplicate of the other arm. e.g. iso Xq is a chromosome with two X long arms and no X short arms.

Isoelectric focussing A technique for separating proteins on the basis of their charge. The mixture of proteins is placed in a gradient of pH across which an electric field is applied. The proteins migrate until they reach the point in the gradient at which they carry no net charge, their isoelectric point.

Isoform Multiple molecular forms of a given protein (or iso enzymes or isozymes if they are enzymes). Isoforms can usually be separated by electrophoresis or some other separation technique. They exist because of multiple gene loci or multiple alleles (also called allelomorphs / allelozymes or allozymes) or subunit interaction or secondary changes - such as post-translational modification.

P a g e | 38 Karyotype The chromosomal constitution of an individual. kb (kilobase) 1000 nucleotides or nucleotide pairs - a unit of single or double stranded nucleic acid length measurement.

Kindred A very extended pedigree.

Kinetochore The part of the centromere to which the spindle fibres are attached.

Label A chemical tag attached to or included within a molecule to enable its subsequent identification. Nucleic acids are conveniently labelled by incorporating radioactive isotopes of phosphorous (32P or 33P) into their sugar phosphate backbones, proteins may be labelled by incorporating a radioactive isotope of sulphur (35S)into methionine residues. Alternatively, fluorescent molecules may be attached via side chains to either nucleotides or to amino acids.

Library A large bank of clones (which may be either genomic or cDNA). The depth of a genomic library is the number of times which any single copy sequence can be expected to be recovered from it.

Line element A dispersed repeat family with tens of thousands of copies, each from 1 to 6 kb long. New elements are generated by retroposition of a transcribed copy.

Linkage The tendency of genes close together on the same chromosome to be inherited together. It can be quantified and used as a mapping tool.

Linkage disequilibrium The occurrence, on the same chromosome, of some combinations of alleles of closely linked genes more often than would be predicted by chance.

Linkage map A map of a chromosome showing distances between loci in terms of the genetic recombination distances between them. See genetic map

Locus Literally, a place. A point on a chromosome or in a genome at which a specific gene or other marker is found. Often taken (wrongly) to mean gene.

Locus heterogeneity see genetic heterogeneity

Lod Score A statistic giving the level of confidence in an estimate of linkage distance between two loci.

Lyonisation See X inactivation.

P a g e | 39 Map position The point at which a marker is found on a genetic map, or at which a clone is found on a cytogenetic map.

Meiosis The sequence of two cell divisions which turns a diploid germ cell into a haploid gamete.

Messenger RNA (mRNA) RNA which leaves the nucleus carrying information which, by translation, will direct the synthesis of polypeptides.

Metaphase The stage of mitosis (or meiosis) at which the chromosomes are at their most condensed and at which they are lined up in the centre of the spindle, about to divide.

Micro array A large number of objects immobilised in a rectangular array on a microscope slide. The objects may be oligonucleotides, DNA from cDNA clones or fragments of genomic DNA. The array can be hybridised with a mixture of two probes labelled in contrasting ways. The ratio of the amounts of each probe which bind to each target on the array is quantified.

Microsatellite A DNA sequence of from 2 to 6 nucleotides which are tandemly repeated from about 5 to 5,000 times (usual range 20 - 50 repeats). A locus containing a microsatellite is often polymorphic because of variation in the repeat number.

Minisatellite A DNA sequence of about 20 to 50 nucleotides which are tandemly repeated from about 5 to 100 times. A locus containing a minisatellite is oftenpolymorphic because of variation in the repeat number.

Missense mutation A mutation which changes the amino acid incorporated into the coded polypeptide chain.

Mitochondrial DNA The DNA of the mitochondrial genome.

Mitochondrial inheritance Inheritance of a character encoded in the mitochondrial genome.

Mitosis A normal cell division resulting in two genetically identical daughter cells.

Monosomy having only one copy of one of the chromosomes.

Monozygotic twins Two individuals derived from a single fertilised egg and therefore genetically identical.

P a g e | 40 Mosaic An individual composed of more than one genetically distinguishable cell population derived from a single zygote. Not the same as a chimaera.

Multifactorial inheritance The occurrence of a phenotype as a result of the action of more than one gene and / or of environmental factors.

Mutagen A physical or chemical factor which increases the mutation rate.

Mutant phenotype A phenotype which is different from the wild type phenotype and which is caused by the possession of one or more mutant alleles.

Mutation A change in DNA sequence from one generation (or cell generation) to the next.

Mutation Rate The frequency with which mutations occur.

Nondisjunction The failure of a chromosome pair to separate at the first meiotic division, or for two chromatids of a replicated chromosome to separate at mitosis(or at the second meiotic division), so that both pass to the same daughter cell.

Nonhomologous chromosomes Chromosomes which are not homologues... See Homologous chromosomes.

Nonsense mutation A point mutation which alters a codon so that instead of coding for an amino-acid it codes for a translation stop signal.

Northern Blot A procedure for measuring the approximate size and abundance of a specific transcript in a complex mixture of transcripts. Named by (humorous?) analogy with Southern blot which it greatly resembles. An RNA population is separated according to size by electrophoresis in an agarose gel, the RNA is transferred to a nylon membrane by blotting and individual RNA species can be identified by hybridisation to a radiolabelled DNA probe and autoradiography.

Nucleosome The basic structural unit of chromatin made up of almost two turns of DNA (146bp) wound around a histone core containing two molecules each of histones H2A, H2B, H3 and H4.

Nucleoside A nucleotide without the phosphate.

Nucleotide A building block of a nucleic acid consisting of a base (adenine, thymine, cytosine, guanine, uracil) joined to a sugar (ribose or deoxyribose) and a phosphate.

P a g e | 41 Null mutation A mutation which leads to the absence of a gene product. obligate heterozygote, obligate carrier An individual who is proved on the basis of pedigree information to carry one copy of a recessive allele even though it cannot be seen in his or her phenotype.

Oligonucleotide A short (2 - 50 nucleotides) sequence of (usually single stranded) DNA which has been chemically synthesised for a specific experimental purpose.

Oncogene A dominant gene whose expression leads to uncontrolled cellular proliferation.

Open reading frame see reading frame p in cytogenetics, the short arm of a chromosome, in biochemistry, protein as in p16 (a 16 kilodalton protein), in population genetics often used for the frequency of the most common of the possible alleles at a locus. (see q) palindrome a double stranded DNA sequence in which the sequence of one strand in the 5´ to 3´ direction is the same as the sequence of the (oppositely orientated)complementary strand in the 5´ to 3´ direction.

PCR see polymerase chain reaction

Pedigree The members of a family, also used to describe a diagram of their relationships one to another and with information on the inheritance of one or more conditions or genetic loci.

Penetrance The frequency with which individuals with the necessary genotype express symptoms of a genetic condition.

Phenocopy An individual in whom a phenotype, normally associated with a mutant gene, has been brought about by some factor in the environment.

Phenotype An individual’s outward appearance (c.f. genotype). It is also used to incluse to describe a cellular or molecular characteristic, e.g. Blood group A andRFLP

Plasmid A short circular DNA sequence which is replicated within a host bacterium (or yeast) and which usually confers a selective advantage (such as antibiotic resistance) to the host. Plasmids have been engineered to serve as vectors for the propagation of DNA which is foreign to the host species.

P a g e | 42 Pleiotropy Multiple, apparently unrelated phenotypic effects of mutation at a single gene.

Point mutation A mutation affecting a single nucleotide pair. It can be used loosely to mean mutations affecting a very small number of nucleotide pairs (perhaps up to the insertion of a small mobile element such as an Alu element) or to the deletion of a small number of nucleotide pairs.

Polyadenylation site The site at the 3´ end of a mRNA at which the mRNA has been cleaved and a tail of 200 - 300 adenosine nucleotides has been added. polygenic inheritance The inheritance of a characteristic which is determined by the cumulative actions of many different genes, each with small individual effects.

Polymerase chain reaction (PCR) A technique by which a relatively small piece of DNA of known sequence can be amplified (often from a complex mixture) by successive cycles of strand separation followed by DNA synthesis (using a DNA polymerase purified from a thermophilic bacterium) primed by artificially synthesised oligonucleotide primers (one for each strand).

Poles The two ends of a spindle where the microtubules converge and to which the chromosomes will eventually be pulled. They form around a structure known as a centriole.

Polymorphism Genetic variation occurring in a population so that at least two alleles are present at a frequency of 1% or gretaer. The variation may range from alteration of noncoding DNA sequence without any phenotypic effect through many possible intermediates to variation which gives rise to a visible change in the visible phenotype.

Polypeptide chain The chain of aminoacids joined by peptide bonds which is the primary product of the translation of the mRNA of a gene.

Polyploid Having more than the normal two haploid sets of chromosomes.

Positional cloning Identification of a gene from no more starting information than its map position in the genome.

Primary constriction see centromere

Primary transcript The unmodified RNA product of gene transcription before splicing has occurred.

P a g e | 43 Proband The affected member in a pedigree through whom the family came to medical / scientific attention.

Probe A DNA or RNA molecule which has been labelled and which may be used to identify its complementary sequence by hybridisation.

Prokaryote A simpler organism than a eukaryote having no nucleus and being different in many other ways too. e.g. a bacterium.

Promoter The DNA sequences at the 5´ end of a gene which are responsible for binding RNA polymerase and transcription factors and which regulate the gene’s expression.

Prophase A stage at the beginning of mitosis or meiosis during which the chromosomes condense and become visible.

Proto-oncogene A gene which may mutate to become an oncogene.

Pseudogene A DNA sequence which resembles a gene but which has been inactivated by mutation so that it cannot produce a functional product.

Pulsed field gel electrophoresis A technique of electrophoresis which is able to resolve very large DNA molecules by periodic alterations of the direction of the applied electric field. q (see p!) in cytogenetics the long arm of a chromosome, in population genetics the frequency of an allele (usually the less frequent of two).

Random mating Selection of a mate without considering their genotype or any trait associated with a particular genotype.

Reading frame The way in which nucleotides are read in groups of three (codons) to specify the polypeptide coded by a gene. An RNA molecule has three possible reading frames - usually the most 5´ AUG codon defines the beginning of the reading frame selected by the ribosomes. An open reading frame contains no in frame stop codons.

Recessive A mutation or allele which does not affect the phenotype unless it is homozygous.

Reciprocal translocation A chromosomal rearrangement in which material is exchanged between two nonhomologous chromosomes.

P a g e | 44 Recombinant A chromosome (or individual) arising from a crossover at meiosis.

Recombinant DNA DNA containing an artificial combination of pieces which are not found together in nature.

Recombination The formation of a new combination of linked alleles by crossover at meiosis.

Recurrence risk The chance that a genetic disease may occur in siblings (or other relatives) of an affected child.

Reduction division The first meiotic division in which the chromosome number is reduced by half.

Repetitive DNA DNA sequences which are repeated more than once in each haploid copy of the genome. See interspersed repetitive DNA, tandemly repeated DNA and satellite DNA.

Restriction endonucleases, (restriction enzymes) Bacterial nucleases which cut double stranded DNA at specific sites defined by short (4- 10bp) usuallypalindromic sequences.

Restriction fragments The (relatively) short fragments of DNA which are the result of the digestion of high molecular weight DNA by a restriction endonuclease.

Restriction fragment length polymorphism (RFLP) A common variation in DNA sequence which manifests itself in the variation in length of one or morerestriction fragments.

Restriction map A map showing the positions of restriction sites within a DNA molecule.

Restriction sites Short, often palindromic DNA sequences which are the sites for recognition by restriction endonucleases.

Retroposition The integration of a sequence derived from RNA into a DNA genome. See retrovirus.

Retrovirus A class of viruses whose infectious genome is single stranded RNA and which, as part of their normal life cycle, integrate into their host genome after conversion of the RNA to DNA by the enzyme reverse transcriptase.

P a g e | 45 Reverse genetics An old name for positional cloning.

Reverse transcriptase A DNA polymerase which takes RNA as its template. It is coded by a retrovirus gene.

(RFLP) See restriction fragment length polymorphism.

Ribosome A ribonucleoprotein complex which translates mRNAs. See your textbooks!

RNA The class of molecules which are the primary products of genes. One type of RNA, mRNA carries the information coded in a gene from the nucleus to the cytoplasm where it is translated into protein. See your textbooks!

RNA polymerase The enzyme which synthesises RNA from a DNA template.

Satellite DNA DNA containing a short sequence of nucleotides (5 - 200 bp) which is tandemly repeated hundreds or thousands of times. see minisatellite andmicrosatellite.

Segregation The separation of the alleles of a pair from each other at meiosis.

Selection The imposition of an external force onto an organism either naturally (Natural selection) or experimentally so that some genotypes survive (and reproduce) better than others.

Sense strand The DNA strand in a gene which has the same sequence as the primary transcript. (see coding strand)

Sex Chromosome One of the chromosomes which are present in different numbers in males and females. In humans this means the X and Y chromosomes, XX in females and XY in males.

Sex-influenced A trait which is expressed to different extents from the same alleles depending on the sex of the individual.

Sex-limited A trait which is not usually sex linked but is only expressed in one sex.

Sex-linked A trait which is caused by mutation of a gene on the X chromosome, usually called X linkage to avoid confusion with Y linked traits.

Sib A brother or sister.

P a g e | 46 Sibship All the brothers and sisters in one family.

Silent allele An allele which has no effect on the phenotype.

Single copy DNA DNA whose sequence is present only once per haploid genome.

Sister chromatid exchange A crossover between sister chromatids (chromatids which are the products of replication of a single chromosome and which ought therefore to be genetically identical).

Somatic cell A cell which is not on the lineage from which gametes are made. (see germline)

Somatic cell genetics The study of genes using hybrids (fusions) between the somatic cells of different species.

Somatic mutation A mutation which takes place in a somatic cell. It may give rise to a clone of descendent cells each of which has inherited the mutation.

Southern Blot A technique named after Prof. Ed Southern in which, after electrophoresis in agarose gels, DNA is transferred to a membrane where it can be analysed by hybridisation with a probe. See blot

Spindle The structure of microtubules which pulls the chromosomes into the daughter cells at anaphase in cell division.

Splice acceptor site The junction between the 3´ end of an intron and the following exon.

Splice donor site The junction between the 3´ end of an exon and the following intron.

Splicing Processing a primary transcript into a mRNA by removal of the introns. It occurs within the nucleus.

Splice junction mutation A mutation which alters a junction between an intron and an exon so that it no longer functions properly. This is likely to have a profound effect on the coded polypeptide, splice donor site mutations lead to the retention of introns in the mRNA, splice acceptor mutations lead to the skipping of the following exon.

Sporadic A case of genetic disease caused by a new mutation.

P a g e | 47 Stop codon One of the three codons (UAA, UAG, UGA) which cause chain termination at the end of translation.

Structural gene A gene coding for a polypeptide or functional RNA product.

STS or Sequence Tagged Site A short region of genomic DNA which has been sequenced and from which a PCR reaction has been designed which will allow its recognition in a DNA sample. STSs play an important role in the construction of clone based maps and in mapping by the use of irradiation hybrids. An EST may be an STS if it can be amplified from genomic DNA. Some STSs contain a polymorphic microsatellite and can thus also be positioned on genetic linkage maps.

Synapsis The close pairing of homologous chromosomes in meiotic prophase which enables crossovers to occur.

Synaptonemal complex The electron dense material which acts as a "zip fastener" to hold together homologous chromosomes in meiotic prophase.

Syndrome A collection of symptoms which occur together and are thought to be caused by the same mutation or chromosomal anomaly.

Synteny The presence of two genes on the same double stranded DNA molecule.

Tandem repeats Repeated sequences which are arranged consecutively and in the same orientation.

Telomere The DNA structure which stabilises the ends of chromosomes.

Telophase The stage of meiosis or mitosis at which the chromosomes have reached the ends of the spindle after division but the daughter cells have not yet taken aninterphase appearance.

Teratogen A substance which can cause malformations of foetuses.

Termination codon see stop codon

Transcription The process of copying DNA into RNA mediated by the enzyme RNA polymerase.

Transfection Transfer of DNA (usually of a gene) into a cultured cell where it can be expressed.

P a g e | 48 Transgenic animal An animal (nearly always a mouse) into the genome of which a foreign gene has been introduced.

Transition A mutation which has changed one purine (A, G) into the other, or one pyrimidine (C, T) into the other. See transversion.

Translation The process of copying a mRNA into a polypeptide chain mediated by the ribosomes.

Translocation A mutation which has moved one segment of a chromosome to a different position in the genome. A reciprocal translocation involves the exchange of material between two chromosomes.

Transversion A mutation in which a pyrimidine is substituted for a purine or vice versa. See transition.

Triploid A cell (or organism) having three haploid copies of the genome.

Trisomy having three copies of a single chromosome

Tumour suppresser gene A gene which if inactivated by mutation allows uncontrolled cellular proliferation. Contrast with oncogene.

Unequal crossing over A crossover in which the chromosomal segments exchanged are not equally sized because the breakpoint has occurred at a different place on each homologue.

Uniparental disomy The inheritance of both copies of a single chromosome from one parent (and neither copy from the other).

Upstream Genes have an orientation which is defined by their direction of transcription (5' to 3'). Upstream means further in the opposite direction to the direction oftranscription of a gene and even possibly beyond its beginning. (Opposite is downstream.)

Vector (in DNA cloning) the molecule (plasmid, bacteriophage or artificial chromosome) used to propagate a cloned DNA fragment.

VNTR (variable number of tandem repeats) A DNA polymorphism caused by the presence of a variable number of short tandem repeated DNA sequences at alocus.

P a g e | 49 Western blot (see blot) Also known as Immunoblot. Proteins blotted onto a membrane post electrophoresis. They can be detected there by appropriate antisera. The name Western blot is a continuation of the Southern blot, Northern blot joke.

Wild type The normal allele at a locus in a population. It is usually a fully functional allele. Equally, the normal phenotype.

X chromosome A chromosome which is present in two copies in the genome of normal human females but in only one copy in normal males.

X inactivation The random inactivation of all but one X chromosome in most cells. See Barr body.

X linked A gene which is present on the X chromosome.

YAC, Yeast Artificial Chromosome A cloning vector based on a the essential components of a yeast chromosome. It provides two telomeres, two selectable markers and an origin of replication.

Y chromosome A small chromosome which, in humans, is present in one copy in males only.

Y linked A gene which is present on the Y chromosome.

Zygote The diploid cell formed by the fusion of two haploid gametes. In humans. a fertilised egg.

P a g e | 50