  MENDELISM IN MAN The Mendelian Principles Probably Applicable to Many Characters of Man.—We are really just beginning to make the proper observations and collect the necessary data with reference to the application of Mendelian principles to the traits of man. Yet brief as has been our study we have disclosed much significant evidence which makes it seem highly probable that many of his characters, good and bad, of mind and body are as subservient to these laws as are the traits and features of lower forms. Davenport and Plate record over sixty human characters or defects which are seemingly inherited in Mendelian fashion. Although about fifty of these are pathological or abnormal conditions, this does not mean that such conditions are more prone to follow Mendelian inheritance but merely that being relatively conspicuous or isolated they are easier to follow and tabulate. Difficult to get Correct Data.—While it must be said that in many cases no simple form of Mendelian tabulation has been unequivocally established, yet the general behavior of the various inheritable traits in question is so obviously related to the conventional Mendelian course that there seems little reason for doubting that they are at bottom the same. Failure to obtain exact proportions may be attributable in part We are handicapped at the outset in man by the many difficulties of getting correct data from the genealogies on which we must depend, or in fact of getting any genealogy at all, for in this country at least, most families keep imperfect records of births and deaths and many of the institutions for the various kinds of defectives have little in their records that will help us in following out hereditary conditions. Then in matters of disease we meet with the fact that many former diagnoses were erroneous. In yet other cases, and this is particularly true among mental and moral defectives, we are often not sure of the paternity of a given child. Furthermore, one is likely to be misled by the proportions which may occur in the very limited number of children of any given couple. Still other difficulties exist. Among these is the fact, for example, that in many cases of defect or susceptibility to disease, a given individual in the stock may have the trait in an expressible and transmissible form, yet it never comes to expression because that individual has been fortunate enough to escape the environmental stimulus which would call it forth. Thus one highly susceptible to tuberculosis might escape infection, or persons hovering on the verge of insanity A Generalized Presence-Absence Formula for Man.—In man as in lower forms some characters or traits are due presumably to the presence of determiners or to their absence. Likewise, dominance and recessiveness are as much in evidence, for in tracing back pedigrees of various traits we find the same forms of tabulation that obtain for these conditions in plants and lower animals hold good. For typical cases in man let us use a generalized presence-absence formula and the arbitrary symbol A for the presence of the determiner of the character (double in the individual, single in the germ) and a for its absence. Thus AA represents a condition in which similar determiners have been derived from both parents and the individual is duplex as regards the character in question; each mature germ-cell will have the determiner. Aa represents a condition in which the individual has received the determiner from only one parent and is therefore simplex with regard to the character; half of the gametes of such an individual will have the determiner and half will lack it. Lastly, aa represents total It is evident that six kinds of gametic matings are possible among individuals representing these various formulÆ. These matings are as follows:
Indications of Incomplete Dominance.—While in cases of strict Mendelian dominance it is not possible Why After the First Generation Only Half the Children May Show the Dominant Character.—If the trait is a simple dominant one it is clear that it will appear in each generation and always spring from an affected individual. By referring back to our tabulation of possible matings on page 100 where the dominant character is represented by the letter A, this can be seen at a glance. If the trait is present in the duplex condition in one parent and absent from the other, then formula 3 applies; all children will show the trait, but in the simplex form (Aa). If the trait is present in the simplex form in one parent and absent in the other, formula 2 applies. Fifty per cent. of the children will have the character in the simplex form (Aa) which means also an even chance of transmitting it to their offspring; fifty per cent. will not inherit it and will be incapable, furthermore, of transmitting it, since they have become nulliplex (aa). In human genealogies if an individual having an unusual trait which is inherited as a dominant marries a normal person and half of the offspring show the trait (and this is common), this means that the parent manifesting the trait had it represented only in the simplex condition, otherwise all of the children would have shown it. Even though the original ancestor who first developed the condition or structure may have had it in a duplex form, it would after the first mating, if this were with an individual lacking the trait, be represented only in the simplex form (see formula 5) and could never become duplex again unless two Eye-Color in Man.—Of normal characters in man which follow the Mendelian formula perhaps eye-color is the best established. Brown or black eye-color is due to a melanin pigment absent from the blue or gray eye. That is, a brown eye is practically a blue eye plus an additional layer of pigment on the outer surface of the iris. The different shades of brown and the black are due to the relative abundance of this pigment. Gray color and the shades of blue seem to be a modification of an original dark blue, due to structural differences in the fibrous tissues of the iris. In inheritance brown or black is dominant to blue or gray, or in other words the presence and absence of a pigment P constitutes a pair of allelomorphs. Hence two brown-eyed parents, if P is duplex in both (or duplex in one and simplex in the other) can have only brown-eyed children. Thus, 1. PP × PP = PP, or all duplex brown. 2. PP × Pp = PP and Pp, half duplex brown and half simplex brown. If each parent has brown eyes but in simplex
If both parents have blue or gray eyes they can not have children with black or brown eyes, since the recessive condition in each parent means total absence of brown pigment in both. If one pair is duplex brown and the other blue, then all children will have brown eyes but of simplex type. If one parent has simplex brown eyes (type Pp) and one blue (pp) then one-half of the children will have brown eyes of simplex type and one-half will have blue eyes. Occasional objections have been raised against the Mendelian interpretation of inheritance in eye-color, but the cases cited in evidence against the theory usually narrow down to those in which the color is so diluted as to render classification uncertain. For example, hazel eyes are sometimes called gray; they belong however to the melanic pigmented type although the brown pigment may be much diluted and occur mainly around the pupil. So-called green eyes are due to yellow pigment on a blue background. In the rare cases where in the same individual one eye is brown and the other blue, the individual should probably be rated as brown-eyed on the supposition that in the one eye the development of brown pigment has in some way been suppressed. In man occasionally a congenital white lock contrasting strikingly with the remaining normally pigmented hair occurs. It behaves as a simple dominant in heredity. Hair-Shape.—Again, straight and curly hair seem to be distinct inheritable characters. Curly is incompletely dominant to straight, the simplex condition yielding wavy hair. Not to enter into details of the matings, statistics gathered by Mr. and Mrs. Davenport show that, two flaxen-haired parents have flaxen-haired children; two golden-haired parents have only golden-haired children; two parents with light brown hair have children with hair of that color or lighter, but never darker; two parents each with dark brown or black hair may have children with all the varieties of hair-color. Fig. 21 Diagram showing descent of brachydactyly through five generations; black symbols indicate affected individuals; ?, male; ?, female (after Farabee). Irregularities.—If a dominant trait or defect depends on more than a single factor, as is sometimes the case, or if it is modified by sex or other conditions, as is true of certain characters, some of which, such as color-blindness, have already been examined, then we shall find some apparently non-affected individuals having affected offspring. Certain diseases, for example, are generally transmitted by affected members of the family to their children in the expected Mendelian ratio for a dominant, yet an occasional skip of a generation may appear in which an apparently perfectly normal individual transmits to his children what, except for the omission in his own case, appears to be an ordinary dominant character. OTHER CASES OF DOMINANCE IN MAN Among other normal characters in man, as far as available evidence goes, dark skin is dominant to light skin; normally pigmented condition to albino; and nervous temperament to phlegmatic. Digital Malformations.—An interesting and easily followed defect is a condition known as brachydactylism, in which the digits are shortened because of the absence or rudimentary condition of one segment. The fingers, therefore, appear to be only two-jointed like the thumb. Several families showing this defect have been charted and it appears to behave as a typical dominant. In looking over such a chart (Fig. 21, p. 106) one is struck by the fact that only half of the children from most of the matings show the defect, but when we recall that the affected parent, after the first generation, probably carried the condition in only the simplex form and married a normal individual, such a result is just what would be expected (see formula 2). Eye Defects.—Congenital cataract is another not uncommon defect in man which is transmitted as a dominant (Fig. 25, p. 112) with occasional irregularities. It is a condition of opacity of the lens of the eye which produces partial or total blindness. In a paper on Hereditary Blindness and Its Prevention, Clarence Loeb (1909) mentions 304 families of which pedigrees have been published. Of the 1,012 children in these families 589, or 58 per cent., were affected. It is obvious that this is near the expected percentage in the case of a dominant trait where matings of affected with normal individuals prevailed. An unfortunate circumstance about this malady from the eugenic standpoint is the fact that it is frequently of the presenile form which comes on late in life so that it is usually impossible to predict whether an individual of marriageable age is immune or will later become affected. Fig. 22 Radiograph (Courtesy of Dr. W. B. Helm) showing polydactyly in a child’s hand. For genealogy of this see Fig. 23, p. 110. Fig. 23 Chart showing a history of polydactylism through five generations in the B—— family. The individual whose hand is pictured in Fig. 22, p. 109, is of the fifth generation. Squares represent males, circles females. Another defect of the eye following the course of a dominant in heredity is a pigmentary degeneration of the retina known as retinitis pigmentosa. Atrophy of the optic nerve is also involved and the final result is blindness. Still another example frequently cited is that of hereditary night blindness (hemeralopia), a disease in which the affected person can not see by any but the brightest light. In most affected families the final outcome is usually total blindness. One of the most remarkable pedigrees of defects in man ever collected is one of this disease published by Nettleship. He succeeded in tracing the defect through nine generations, back to the seventeenth century. The genealogy includes 2,116 persons. The character behaves as a single dominant in males, but frequently, though Fig. 24 Radiograph (Courtesy of Dr. W. B. Helm) showing a partial syndactyly in each hand of an individual. Some degree of webbing between the more distal portions of the affected parts is usual. Fig. 25 Pedigree of a family with presenile cataract (black symbols); numbers in circles indicate unaffected individuals (after Davenport). Other Defects Inherited as Dominants.—Not to go into details other defects which behave as dominants or modified dominants in human inheritance may be mentioned. The following list is not complete and it must be understood that in some cases the statistics are insufficient to justify us in making anything but a tentative decision. We may thus enumerate as dominant As a final illustration of a serious malady in man which acts as a dominant in inheritance, let us take Huntington’s chorea. Ordinary chorea, or St. Vitus’ dance, a disorder characterized by involuntary muscular movements, is commonly though not always confined to children and usually ends in recovery, but Huntington’s chorea appears typically in middle life and is a much more dangerous malady. Fig. 26, p. 114, represents the family history of one of five cases which have been studied by Doctor Lorenz in the Mendota Hospital for the Insane. All charts which have been platted of this malady show it to be inherited as a dominant. This means that half of the children of an individual who carried the malady in the simplex condition, and all the children of one who carries it in the duplex condition, are probably marked for this terrible end. And the true horror of it can only be appreciated by one who has seen the last stages of the malady. The victim once in its grasp gradually becomes wrecked in mind and body; the muscular twitchings and disorders of movement continually increase and dementia progresses until at last death ensues. Fig. Fig. 26 Chart showing descent of Huntington’s chorea in the P—— family (courtesy of Dr. W. F. Lorenz). Squares represent male, circles female; shaded figures are choreic members of the family; partially shaded figures, slightly affected or very “nervous” members. The members of the last generation are for the most part still too young to show their condition. The cross indicates the individual in the asylum from whom the record was traced back. CASES OF RECESSIVENESS IN MAN Recessive Conditions More Difficult to Deal With Because They Are Frequently Masked.—Coming now to the question of recessive conditions in man, we find that defects are more likely to be of recessive than of dominant type. Apparently normality usually means the presence of normal determiners and abnormality, the absence of some essential determiner. In the latter case, a unit-factor has seemingly been lost out in some way in the germ-plasm, and the product of such germ-plasm is therefore incomplete. As long as the loss is counterbalanced by the presence of a single determiner from the other line of ancestry, that is, as long as the simplex (Aa) condition prevails, the loss may not be in evidence, except in cases of incomplete dominance (taints, etc.), but any mating which permits of the production of the nulliplex condition will bring the defect to expression again. Fig. 27 Chart showing inheritance of Huntington’s chorea in the R—— family (courtesy of Dr. W. F. Lorenz); 1, 2 have been patients at Mendota Hospital for the Insane; 3, died of “paralysis”; the fourth or last generation indicated by the cross, ranging in age from 6 to 14, are too young yet to show their condition as regards this malady. The obscure nature of recessives makes such conditions more difficult to deal with than dominant defects. For as regards the latter we have seen that marriage of unaffected members of the family as far as that particular trait is concerned, is perfectly safe, even to a cousin, for once the germ-plasm is purged of such a positive factor, it, in so far as we know, remains pure. But in the case of a recessive character due to the absence of some necessary determiner a normal offspring of simplex constitution (Aa) will probably transmit to half of his children the capacity for handing on the defect, or if mated to another normal individual of simplex constitution (Aa) is likely to have the actual defect revealed again in one-fourth of his children and latent in two-thirds of the remainder. Albinism a Recessive.—As an easily understood illustration of this type of case we may take human albinism, a condition which is due to the absence of a pigment-developing determiner. According to Davenport the albinic condition is recessive to normal condition. If albino (aa) is mated with albino (aa) nothing but albino children may be expected. An albino (aa) mated with a normal individual will have normal Other Recessive Conditions in Man.—If for albinism we substitute certain forms of insanity, hereditary feeble-mindedness (Fig. 28, p. 118), or hereditary epilepsy, all of which apparently follow the same law, we can readily understand how unfit such matings are where both strains are affected. Marriage with similarly defective stock will result in the affection appearing in one-fourth of the progeny, and one-half of them, though apparently normal themselves, will have the capacity for transmitting the imperfection. It is in the existence of such hidden factors that the chief danger in the marriage of cousins, or in fact any consanguineous marriage lies. A few of the various defects which seem to be inherited as recessives when mated with normality are: susceptibility to cancer; chorea (St. Vitus’ dance); true dwarfism (all parts proportionately reduced); Alkaptonuria (urine darkens after passage); alcoholism and criminality, where based on mental deficiency; hereditary hysteria; multiple sclerosis (diffuse degeneration of nervous tissue); Friedreich’s disease (degeneration of upper part of the spinal cord); Merriere’s disease (dizziness and roaring in ears); Of non-pathological conditions in man which are inherited as recessives, apparently either very great or very small intellectual ability are examples. Fig. 28 Chart showing descent of feeble-mindedness as a typical recessive (after Goddard). Squares represent males, circles females; DD, homozygous dominant; DR, heterozygous dominant (i. e. normal although a carrier); RR, pure recessive; N, normal; F, feeble-minded; A, alcoholic. Breeding Out Defects.—Even though recessive defects occur in a stock, there is the possibility of diluting out the imperfection in successive generations if care is taken always to marry into a stock wholly free from it. For example, a normal individual carrying a recessive defect will bear the abnormality in half of his or her germ-cells. This means that when such an individual marries a normal, non-carrier, half of their children will be wholly normal (AA) and half will be carriers; normal but of simplex constitution (Aa). If now this generation, The proportion in which the recessive defect would appear in successive generations if all persons in a given generation married only normal individuals who were non-carriers is indicated in the following table where AA indicates a normal individual, Aa one who is normal but a carrier, and aa an individual with the imperfection expressed; to indicate proportions simply after the first generation, four is arbitrarily chosen as the number of children which results from each marriage:
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