Human Genetics and McKusick's Mendelian Thomas R. Mertens is professor of biology at Ball State Univer- sity, Muncie, IN 47306, where he has been on the faculty since In h rita nc pr1957. He activehas in NABT been for many years and served as its president in 1985. Since 1960, Mertens has been involved in NSF- funded teacher education projects for secondary school biology teachers. Over the past decade he and colleagueJon Hendrixhave inZ M an>XZ operated seven NSF-funded teacher education workshops on human genetics and bioethicaldecision-making. Mertens has pub- lished frequentlyin various science education journals and in the Journalof Heredity.He co-authoredHuman Genetics (4th ed.), pub- lished by Charles E. MerrillPublishing Co., Columbus, OH, and Downloaded from http://online.ucpress.edu/abt/article-pdf/50/5/262/43408/4448732.pdf by guest on 28 September 2021 GeneticsLaboratory Investigations (8th ed.), published by Burgess Publishing Co., Minneapolis, MN. Mertens has received NSTA's Ohaus Award for InnovativeCollege ScienceTeaching and its Dis- Thomas R. Mertens tinguished Service to Science EducationCitation. Dr. Victor A. McKusick, university professor of 2,200 autosomal dominant, more than 1,400 auto- medical genetics at The Johns Hopkins University somal recessive and more than 280 X-linked pheno- School of Medicine, is a world-renowned medical re- types. The data in Table 1 show how the book has searcher and prolific author. grown during the 20 years it has been published. The One of his best known and most widely used increases in the number of phenotypes listed in each books is MendelianInheritance in Man, Catalogsof Au- edition of the book reflect the rapid advances made tosomalDominant, Autosomal Recessive, and X-Linked in human and medical genetics over the last two de- Phenotypes,published by The Johns Hopkins Univer- cades. sity Press. First published in 1966, McKusick's cat- Each entry in the catalog is assigned a five-digit alog was released in its seventh edition in the fall of number. In the 1986 edition, the numbers for domi- 1986. While the 47 prefatory pages and 1,741 textual nant traits begin with 10005 and end with 19447;re- pages of this massive volume are obviously intended cessive traits are numbered from 20010 to 27900, and for medical professionals and genetics researchers, X-linked traits from 30002 to 31500. Each entry in- the book is a gold mine of useful information for cludes alternate names given to the genetic condi- those of us who teach biology. The inservice high tion, a discussion of the condition and a list of perti- school biology teachers who are in my classes and nent literature,including those items cited in the dis- workshops always enjoy spending some time ex- cussion of the disease or defect. amining it. Preceding the number of a particularentry in the As a teacher of general and human genetics, I find catalog may be an asterisk. The asterisk means that McKusickto be an invaluable reference. Hardly a day in McKusick's judgment the method of inheritance goes by when I do not turn to it to help me answer a (e.g., autosomal dominant) is well established and question that arises in the classroom or in my office the phenotype described in the entry is determined when students and others come to me for informa- by a gene locus that is separate from those repre- tion. The purpose of this article is to inform readers sented in other entries in the catalog. When no as- about the McKusickcatalog and what can be learned terisk precedes the entry number, the method of in- from it. In addition, I will attempt to give examples of heritance is not firmly established but only suspected information gained from McKusick that have been and/or the uniqueness of the gene locus involved is useful in my teaching. Perhaps some readers may be not clear. convinced that the school library should spend the In the current edition, McKusick includes 1,172 money to purchase a copy of this useful reference well documented autosomal dominant conditions book. plus 1,029 less well established;610 well documented autosomal recessives plus 810 less well verified; and What is the McKusick Catalog? 124 asterisked X-linked traits plus 162 without as- terisks. Thus, the total of 3,907 phenotypes includes In the current edition of his book, McKusick cat- 1,906 marked with an asterisk and 2,001 not so desig- alogs more than 3,900 phenotypes, including nearly nated. 262 THE AMERICAN BIOLOGY TEACHER, VOLUME 50, NO. 5, MAY 1988 the equivalent of 5,523 codons. The mitochondrion's Table 1. The number of gene loci identified by Mendelizing phenotypes (modified from McKusick,1986). most important function is oxidative phosphoryla- fion, a process that is under the regulation of both Mechanism of Year* mitochondrial Inheritance 1966 1968 1971 1975 1978 1983 1986 nuclear and DNA. McKusick says that 13 of the 69 known polypep- Autosomal 837 793 943 1218 1489 1827 2201 tides involved in oxidative phosphorylation are en- Dominant Autosomal 531 629 783 947 1117 1298 1420 coded by mitochondrial DNA. In addition, genes Recessive specifying tRNAs and rRNAs involved in the syn- X-Linked 119 123 150 171 205 243 286 thesis of protein within the mitochondrion are also TOTALS 1487 1545 1876 2336 2811 3368 3907 mapped on chromosome M. Certain human genetic * Data based on McKusick'scatalog for the year indicated. disorders thought to be associated with mitochon- drial mutations are also mentioned by McKusick. In the 47 prefatory pages McKusickhas included a Whatgene loci areassigned to whichchromosomes? variety of additional kinds of information, not the Knowing that the gene for the Rhesus (Rh) blood least of which is interesting historicalbackground on group has been assigned to chromosome #1 Downloaded from http://online.ucpress.edu/abt/article-pdf/50/5/262/43408/4448732.pdf by guest on 28 September 2021 the evolution of human and medical genetics over somehow makes discussion of this trait more specific the last two decades. The prefatory pages also in- and concrete. Furthermore,as the instructor,you can clude valuable appendices: tables listing the funda- say with confidence that the Rh factor gene assorts mental biochemical (often enzyme) defect associated independently of the gene for the ABO blood group, with each of those genetic conditions for which it is since the ABO gene has been assigned to chromo- known; extensive data on the human gene map some #9. Thus, using Rh and ABO in a ex- what genes are on which chromosomes and what teaching ample will permit demonstration of Mendel's method was used to establish the second gene's location; law. and lists of human cell cultures available for specific genetic diseases. Similarly,McKusick's prefatory appendices list the specific chromosomal location of many other genes of interest. For example, the gene for nail patella How Can Biology InstructorsUse the Book? syndrome (McKusickno. 16120),an autosomal domi- nant trait, is also located on chromosome #9 and Now that you have some understanding of what is has been shown to exhibit linkage to the ABO included in McKusick'sMendelian Inheritance in Man, locus. These two gene loci can be used to let us turn our attention to how biology instructors illustrate the con- cepts of linkage and crossing over; can use it to update their teaching and ensure the McKusick indi- cates that there is about 10 percent accuracyof the information they present. recombinationbe- tween these genes. How manylinkage groups are therein humans? Whatbiochemical defect is the causeof a particulargenetic A linkage group consists of all the genes located on diseaseor defect? a particular chromosome. Since garden pea plants have 2n = 14 (7 pairs of chromosomes), the garden Consider the following examples, all taken from pea has seven linkage groups. By the same token, McKusick:alkaptonuria, one of the first inborn errors the fruit fly Drosophilamelanogaster has four linkage of metabolism studied in humans, is caused by a de- groups; maize (Indian corn) has 10; and humans fect in the enzyme, homogentisic acid oxidase. would be expected to have 23 linkage groups-one Classic phenylketonuria (PKU) is caused by a defect for each of the 22 autosomes plus one for the X chro- in the enzyme, phenylalanine hydroxylase. A defi- mosome. ciency in FactorVIII in the blood clotting sequence is Imagine students' chagrin when they are told there associated with both classic X-linked hemophilia A are 25 linkage groups in humans. How can this be? (McKusickno. 30670) and with Von Willebranddis- Where can information be found on the two "extra" ease (McKusickno. 19340), an autosomal dominant linkage groups? McKusick comes to the rescue by trait. Many other specific but perhaps less well discussing (in the prefatory pages of his book) the known examples of established biochemical defects gene map of the Y chromosome and the gene map of can be found in an appendix in McKusick'sbook. chromosome M. Because the Y chromosome is largely not homolo- How else canMcKusick's book aid in classroomand labora- gous with the X, genes occurring on it are uniquely tory instruction? Y-linked, thus constituting a separate 24th linkage McKusick's catalogs are useful inl verifying the group. Chromosome M is the mitochondrialor 25th method of inheritance for the diverse examples of chromosomes; it consists of 16,569 DNA base pairs, human traits cited by the authors of biology text- 264 THE AMERICAN BIOLOGY TEACHER, VOLUME 50, NO. 5, MAY 1988 books and laboratory manuals. Previous research Table 2. A sample of human traits of possible interest for (Barnes & Mertens 1976) has shown that some ex- classroom and laboratoryinstruction.