Hereditary persistence of hemoglobin F (HPHF)
equal crossing over between a mispaired delta and beta cistron. hemoglobin S a hemoglobin with a glutamic acid replaced by a valine at position 6 of the beta chains. The substitution replaces a charged side chain with a hydrophobic residue, and this results in a hydro- phobic patch on the surface of the molecule. This patch can fit into a pocket in an adjacent hemo- globin S, and therefore adjacent molecules stack up to form fibers that deform the cell. The stacking only occurs when hemoglobin is in the deoxyge- nated state, and it occurs to only a minor degree in the cells of heterozygotes. Misshapen red blood cells in venous blood are a diagnostic feature of sickle-cell anemia (q.v.). See Appendix C, 1949, Pauling; 1957, Ingram; 1973, Finch et al.; gene, sickle-cell trait. hemoglobinuria the excretion of hemoglobin in solution in the urine. hemolysis the rupturing of blood cells. hemolytic anemia See anemia. hemophilia a hereditary disease characterized by a defect in the blood-clotting mechanism.
Hemophilia was the first human trait recognized to show sex- linked inheritance. Hemophilia A (classical hemo- philia) is due to a deficiency of functional antihe- mophilic factor (factor 8). Hemophilia B (Christmas disease) results from a deficiency of plasma thrombo- plastin component (factor 9). The clotting factors are proteins encoded by genes (HEMA and HEMB) that reside at a considerable distance from one another on the X chromosome. The hemophilic population consists of hemizygotes for HEMA and for HEMB in a ratio of 4 : 1.
The hemoglobin genes have also mu- tated in various domesticated animals, since hemo- philia A occurs in cats, dogs, horses, and sheep, and hemophilia B is known in cats and dogs. See Appen- dix C, 1820, Nasse; 1988, Kazazian et al.; anti-hemo- philic factor, blood clotting, HEMA, HEMB, plasma thromboplastin component, royal hemophilia, von Willebrand disease. http://www.hemophilia.org. hemopoiesis See hematopoiesis. hemopoietic See hematopoietic. hemopoietic histocompatibility (Hh) used in ref- erence to transplantation of bone marrow in inbred strains of mice and their hybrids. As measured by the growth of the transplanted marrow cells in the spleen, a unique form of transplantation genetics seems to apply whereby hybrid recipients resist pa- rental bone marrow grafts, but parental recipients accept hybrid bone marrow. hemozoin a non-toxic form of hemoglobin depos- ited in the food vacuole of the Plasmodium tropho- zoite (q.v.). See malaria, vacuoles. herb a plant with no persistent parts above ground, as distinguished from a shrub or tree. herbage herbs collectively, especially the aerial portion. herbarium a collection of dried and pressed plant specimens. herbicide a chemical used to kill herbaceous plants.
See Roundup. herbivore a plant eater. hereditary disease a pathological condition caused by a mutant gene. See Appendix C, 1966, McKusick, human genetic diseases. hereditary growth hormone deficiencies a defi- ciency in human growth hormone (q.v.) often due to deletions or point mutations at the GH1 locus. Deletions result in severe dwarfism by 6 months of age. hGH replacement is initially beneficial, but anti-hGH antibodies subsequently develop and may arrest the response to exogenous hGH. The lack of immunological tolerance to hGH occurs because the mutant fetus never produced hGH during the period when its immune system was being programmed not to respond to self-proteins. In cases where a biologi- cally inactive, mutant hGH is produced, treatment with synthetic hGH is usually effective. See human growth hormone gene, human growth hormone re- ceptor. hereditary hemochromatosis See hemochroma- tosis.
hereditary nonpolyposis colorectal cancer (HNPCC) a human cancer syndrome due to mutations in the MSH2 gene. This gene has been mapped to 2p22- p21, and it encodes an enzyme that functions in mis- match repair (q.v.). hereditary persistence of hemoglobin F (HPHF) the continued synthesis of fetal hemoglobin in adults. One form of HPHF results from large dele- tions that remove the δ and β globin genes from chromosome 11. Under these circumstances, the Gγ
Hereditary spherocytosis (HS)
and Aγ genes are switched on and γ globin chains are synthesized. In the nondeletion form of HPHF, missense mutations have been found 158-202 base pairs upstream of the Gγ chain ORF. These base substitutions presumably prevent a control element from switching off production of gamma chains. See Appendix C, 1984, Collins et al.; hemoglobin, hemo- globin genes. hereditary spherocytosis (HS) a highly variable genetic disorder affecting the red blood cell mem- brane and characterized by anemia (q.v.), jaundice (q.v.), enlargement of the spleen, and hemochro- matosis (q.v.).
HS results from a defect or deficiency in one of the cytoskeletal proteins associated with the erythrocyte membrane.35%-65% of all HS cases are associated with mutations in the ANK1 gene, and this form of HS is also called ankyrin-1 deficiency, ankyrin-R deficiency, or erythrocyte ankyrin deficiency. Erythrocytes in HS patients are smaller, rounder, and more fragile than normal, get trapped in narrow blood vessels, particularly in the spleen, and hemolyze, resulting in HS symptoms. This dis- order is most common in people of northern Euro- pean ancestry. See ankyrin.
heredity a familial phenomenon wherein biologi- cal traits appear to be transmitted from one genera- tion to another. The science of genetics has shown that heredity results from the transmission of genes from parents to offspring. The genes interact with one another and with their environment to produce distinctive characteristics or phenotypes. Offspring therefore tend to resemble their parents or other close relatives rather than unrelated individuals who do not share as many of the same kinds of genes.
heritability an attribute of a quantitative trait in a population that expresses how much of the total phenotypic variation is due to genetic variation. In the broad sense, heritability is the degree to which a trait is genetically determined, and it is expressed as the ratio of the total genetic variance to the pheno- typic variance (VG/VP). In the narrow sense, herita- bility is the degree to which a trait is transmitted from parents to offspring (i.e., breeding value), and it is expressed as the ratio of the additive genetic variance to the total phenotypic variance (VA/VP). The concept of additive genetic variance makes no assumption concerning the mode of gene action in- volved. Heritability estimates are most commonly made by (1) regression-correlation analyses of close relatives (e.g., parent-offspring, full sibs, half sibs), (2) experiments involving response to selection, and (3) analysis of variance components. Traits with high heritabilities respond readily to selection.
hermaphrodite an individual having both male and female reproductive organs. A simultaneous her- maphrodite has both types of sex organs throughout life. A sequential hermaphrodite may have the ovary first (protogyny), to be replaced by a testis later, or may develop the testis first (protandry), to be re- placed later by an ovary. See consecutive sexuality, sperm sharing. herpes virus one of a group of animal viruses hav- ing a duplex DNA molecule within an icosahedral capsid.
They range in size from 180 to 250 nanome- ters and produce internuclear inclusions in host cells. If the virus infects humans, the acronym is given an initial “H.” HHV1 (herpes simplex virus) causes cold sores. HHV2 (genital herpes virus) causes lesions and is sexually transmitted. HHV3 (varicella zoster virus) causes chicken pox and shingles. See enve- loped viruses, Epstein-Barr virus (EBV), human cyto- megalovirus (HCMV), human papillomavirus, virus. Hers disease a hereditary glycogen storage disease in humans arising from a deficiency of the enzyme hepatic phosphorylase.
It is inherited as an autoso- mal recessive trait with an incidence of 1/200,000. het a partially heterozygous phage. heterauxesis the relation of the growth rate of a part of a developing organism to the growth rate of the whole or of another part. If the organ in question grows more rapidly than the organism as a whole, it shows tachyauxesis; if less rapidly, bradyauxesis; if at the same rate, isauxesis. See allometry. heteroalleles alternative forms of a gene that dif- fer at nonidentical muton sites. Intragenic recombi- nation between mutant heteroalleles can yield a functional cistron. Compare with homoalleles.
See Appendix C, 1955, Pritchard; 1962, Henning and Yanofsky. heterobrachial inversion pericentric inversion. hetrocapsidic virus See segmented genome. heterocaryon heterokaryon. heterochromatin chromosomal material that, un- like euchromatin (q.v.) shows maximal condensation in nuclei during interphase. Chromosomal regions behaving in this way are said to show positive hetero- pycnosis. When entire chromosomes (like some Y chromosomes) behave this way, they are called het- erochromosomes. In polytene chromosomes, hetero- chromatic regions adjacent to the centromeres of all chromosomes tend to adhere, forming a chromo- center. Heterochromatin is composed of repetitious DNA, is late to replicate, and is transcriptionally in-
active. Such heterochromatic segments are often called constitutive to distinguish them from chromo- somal segments or whole chromosomes that become dense and compact at different developmental stages. In such cases, one homologous chromosome may behave differently from the other. An example is the condensed, inactivated X chromosome charac- teristic of the diploid somatic cells of mammalian fe- males. Such chromosomes are sometimes said to contain facultative heterochromatin, although there is no evidence that they contain a type of DNA differ- ent from euchromatin.
The relative amounts of het- erochromatin in each chromosome are shown in the Drosophila melanogaster entry. The pericentric het- erochromatin is underreplicated in the polytene chromosomes of Drosophila, and this underreplica- tion is under genetic control. See Appendix C, 1928, Heitz; 1936, Schultz; 1959, Lima-de-Faria; 1970, Pardue and Gall, 1998, Belyaeva et al.; centromere, euchromatin, position effects. heterochromatin protein 1(HP1)a nonhistone protein that binds to heterochromatin and to the telomeres of Drosophila polytene chromosomes. It is a highly conserved protein with homologs in yeast, plants, and mammals.
HP1 is required for the proper segregation of chromosomes during mitosis in em- bryos. It can enter nuclei and bind to specific chro- mosomal sites where it causes localized condensa- tion of DNA and represses the transcriptional activity of neighboring genes. The gene Suppressor of variegation 205 encodes HP1. It is located on the left arm of chromosome 2 at 31.1. Loss of function mu- tant alleles are recessive lethals and cause end-to-end fusions of telomeres. Reduced function alleles cause variegation. See Appendix C,1986, James and Elgin. heterochromatization the situation where euchro- matic chromosome regions acquire the morphology of heterochromatin when juxtaposed to heterochro- matin. See Appendix C, 1939, Prokofyeva-Belgov- skaya; position effects heterochromosome See B chromosomes, hetero- chromatin. heterochronic genes genes whose products are re- quired for the timing of specific developmental events.
Mutations in these genes disrupt the tempo- ral pattern of development and can also lead to phy- logenetic variation. In Caenorhabditis elegans muta- tions in single heterochronic genes affect the timing of cell division and differentiation in different post- embryonic cell lineages (without affecting other lin- eages), resulting in the generation of cell patterns normally associated with earlier or later develop- mental stages. Two of the heterochronic genes in C. elegans, lin-4 and let-7, encode small temporal RNAs (q.v.), which control developmental timing by inhib- iting the translation of target messenger RNAs.
Other heterochronic genes affect the timing of neu- roblast proliferation (Drosophila), scale cell matura- tion (Papilio), sporulation (Dictyostelium), post-em- bryonic shoot development(maize), and flower formation(Arabidopsis). In many eukaryotes the timing of many developmental events is controlled by hormones, and numerous genes affecting hor- mone function have been described. However, little is known about what controls the timing of hormone secretion. See Appendix C, 1984, Ambros and Hor- vitz; heterochrony. heterochrony a change in the timing of a develop- mental event (e.g., time of appearance of a morpho- logical trait or of expression of a gene) relative to other developmental event(s).
Heterochrony has been well documented at the genetic and molecular level in Caenorhabditis elegans, where mutations in known heterochronic genes (q.v.) result in preco- cious or retarded development in specific post- embryonic cell lineages. In addition to its role in regulating the temporal pattern of development, heterochrony is thought to be a major force for phy- logenetic variation (e.g., variation between an an- cestral and descendant species). A commonly cited example of heterochrony is neoteny (q.v.) in Ambys- toma mexicanum (q.v.).
The sexually mature adult of this aquatic salamander is a chimera (q.v.) consisting of adult and larval tissues (including gills), compared to the adult of the land-dwelling species. This is due to a genetic defect in thyroid hormone production, which retards the maturation of juvenile somatic tis- sues relative to gonadal tissues. The term heteroch- rony was originally coined by the German physician and biologist, Ernst Haeckel (1834-1919), but has evolved over the years to its present form. heterocyclic referring to any organic compound forming a ring made up of carbon atoms and at least one atom other than carbon.
Examples of heterocy- clic amino acids are proline, hydroxyproline, trypto- phan, and histidine (see amino acid). Purines and py- rimidines are heterocyclic compounds (see bases of nucleic acids). The porphyrin portion of heme is made up of heterocyclic rings (see heme). heterodimer a protein made up of paired polypep- tides that differ in their amino-acid sequences. heterodisomy See disomy. heteroduplex 1. a DNA generated during genetic recombination by base pairing between complemen- tary single strands from different parental duplex
molecules. 2. a double-stranded nucleic acid in which each chain has a different origin and therefore is not perfectly complementary; e.g., the hybrid molecule generated by in vitro annealing of eukaryo- tic mRNA with its DNA. See Appendix C, 1969, Westmoreland et al. See R-loop mapping. heteroecious referring to a parasite requiring two or more hosts to complete its life cycle, as with some rust fungi and insects. heterofertilization double fertilization of angio- sperms in which the endosperm and egg are derived from genetically different sperm nuclei. heterogametic sex the sex that produces gametes containing unlike sex chromosomes (e.g., male mam- mals produce X- and Y-bearing sperm, usually in equal proportions). Crossing over is often suppressed in the heterogametic sex.
See Appendix C, 1912, Morgan; 1913, Tanaka. Compare with homogametic sex. heterogamy the alternation of bisexual reproduc- tion with parthenogenetic reproduction. heterogeneous nuclear RNA (hnRNA) the pool of extrachromosomal RNA molecules found in the nu- cleus, consisting of a heterogeneous mixture of pri- mary transcripts, partly processed transcripts, dis- carded intron RNA, and small nuclear RNA. The term is often used to refer to the primary transcripts or to their modified products alone. See Appendix C, 1961, Georgiev and Mantieva; posttranscriptional processing, spliceosome, Usn RNAs.
heterogenetic antigens the same or similar (cross- reacting) antigens shared by several species Forssman antigen, q.v.). Antibodies produced against one of these antigens will also react with the other antigens of the system even though these are derived from a different species; such antibodies are also called heterophile antibodies. See heterophile antigen. heterogenote See heterogenotic merozygote. heterogenotic merozygote a partially heterozy- gous bacterium carrying an exogenote containing al- leles differing from those on the endogenote. heterogony cyclical parthenogenesis, when one or more parthenogenetic generations alternate with an amphimictic one, usually in an annual cycle. Aphids, gall wasps, and rotifers are examples of animals un- dergoing heterogony. heterograft a graft between members of different species; also known as a xenograft. Compare with al- lograft, isograft. heterokaryon a somatic cell that contains nuclei derived from genetically different sources.
The nu- clei do not fuse, but divide individually and simulta- neously to form new cells, as commonly occurs in fungal hyphae. Ciliate protozoans, such as Tetrahy- mena, may be functional heterokaryons, if they carry a drug-resistant gene in the transcriptionally inac- tive, diploid, germinal micronucleus and a drug-sen- sitive allele in the transcriptionally active, highly polyploid, somatic macronucleus. See interspecific heterokaryon. heterokaryon test a test for organelle mutations based upon the appearance of unexpected pheno- types in uninucleate cells derived from specially marked heterokaryons. For example, suppose that heterokaryons form between colonies thought to carry a mitochondrial mutant (A) and colonies car- rying a known nuclear mutation (B).
If uninucleate progeny cells or spores exhibiting both the A and the B phenotypes can be derived from the hetero- karyons, then the A mutation is probably in an ex- tranuclear gene, because recombination of nuclear genes does not occur in heterokaryons. heterokaryosis the condition in which fungus hy- phae contain haploid nuclei of different genotypes, as a result of nonsexual fusion of the different types of hyphae. heterokaryotypic referring to an individual carry- ing a chromosomal aberration in the heterozygous condition. heterologous 1. in immunology, referring to an antibody and an antigen that do not bind to one an- other; either may be said to be heterologous to the other. 2. in transplantation studies, referring to a graft originating from a donor belonging to a species different from the host’s. 3. in nucleic acid studies, referring to a DNA of a different source from the rest. Thus, a rabbit hemoglobin gene used as a probe to detect a hemoglobin gene from a mouse gene li- brary represents heterologous DNA. 4.
In transpo- son tagging (q.v.), the use of a transposon from one species to tag a gene from another—for example, us- ing the maize Activator transposon to tag and clone a gene conferring disease resistance in tobacco. heterologous chimera a chimera (q.v.) formed by cells or tissues from two different species. heteromeric See heteropolymeric protein. Heterometabola Hemimetabola (q.v.). heteromixis in fungi, referring to the mating sys- tem where sexual reproduction involves the fusion.