Being Well Born Part 6

THE PLACE OF THE MENDELIAN FACTORS IN THE GERM-CELLS

=Parallel Between the Behavior of Mendelian Factors and Chromosomes.--=The question arises as to whether there is any evidence from the study of germ-cells themselves to bear out the Mendelian conception of separation of contrasted characters in the gametes of the F_{1} generation. In the discussion of the maturation of germ-cells (Chap. II) it has already been seen that the chromosomes of the germ-cells are in all probability arranged in h.o.m.ologous pairs, one member being of maternal and the other of paternal origin, and that furthermore they are closely a.s.sociated with the phenomena of heredity. And since in maturation there is an actual segregation of the chromosomes into two sets, half going to one cell and half to its mate, a physical basis adequate to the necessities of the case is really at hand. It will be recalled that the individuals of a pair separate in such a way at the reduction division that the paternal member goes to one cell and the maternal member to the other, although each pair seemingly acts independently of the others with the result that any mature germ-cell may contain chromosomes from each of the original parents but never the two chromosomes which earlier made up a pair. The close parallel between the behavior of chromosomes and the behavior of Mendelian factors, although the two sets of phenomena were discovered wholly independently of each other, is obvious. If we suppose that each chromosome bears the determiner of a Mendelian character and that chromosomes bearing allelomorphic characters make up the various pairs which are seen in the early germ-cells of an individual before reduction occurs, then the segregation of the individuals of an allelomorphic pair into different gametes must result in consequence of the pa.s.sing of the corresponding chromosomes into separate gametes. Fig. 20, p. 95, from Professor Wilson represents equally well the segregations of pairs of chromosomes or pairs of Mendelian characters.

[Ill.u.s.tration: FIG. 20

Diagram showing union of factors from the two separate parents in fertilization and their segregation in the formation of germ-cells (after Wilson). With four pairs of factors (_Aa_, _Bb_, _Cc_, _Dd_), sixteen types of gametes are possible, as shown in the series of small circles at the right. The same diagram equally well represents the pairings and segregations of chromosomes.]

=A Single Chromosome not Restricted to Carrying a Single Determiner.--=It has been objected that there may be more pairs of independently heritable allelomorphic characters than there are pairs of chromosomes. It is true that there are more pairs of characters than pairs of chromosomes but there is no reason for supposing that a given chromosome is restricted to carrying a single unit-determiner. On the contrary it probably carries several or many. Some workers have pointed out that certain units might be interchanged during the pairing of chromosomes before the reduction division, others that inasmuch as the chromosomes become diffuse and granulated during the intervals between divisions it is not improbable that the individual units may become separated from their original system during such times and that it is a matter of chance into which of the h.o.m.ologous chromosomes, A or a, they enter with the re-establishment of the chromosomes. On the other hand, cases are known where two or more separate characters are permanently a.s.sociated in inheritance, that is, if they enter a crossed form together they come out together in the grandchildren as if they were carried in the same unit-body in the germ-cell. The only observable unit-bodies that fulfil the necessities of such cases are the chromosomes. This tendency of characters to exist in groups which are inherited independently of one another is coming more and more into evidence as we penetrate farther into the intricacies of inheritance, and it is exactly what we would expect on the supposition that each chromosome carries the determiners of a number of characters instead of a single one.

CHAPTER IV

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 p.r.o.ne 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 to the probability that what we loosely regard as a character should in reality be a.n.a.lyzed into more elemental components, and above all to the fact that from the very nature of the conditions under which human records must be obtained, there is considerable chance of inaccuracy or error in such accounts. How many human traits follow Mendelian rules remains largely for future investigators to establish.

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 inst.i.tutions 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 might never receive the precipitating stimulus which would topple them into actual insanity; yet each would be wrongfully recorded in a genealogy looking to such traits as perfectly normal. Or again if it be a question of intellectual brilliancy as shown by accomplishment in the realm of scholarship, or of worldly affairs, the ones who although possessing them have had no chance to display unusual talents would be tabulated as average whereas in fact they should be recorded as of high rank. That this is particularly likely to happen in the case of women is evident.

=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 absence of the determiner. Such an individual is _nulliplex_. He or she will not have the determiner represented in any of the gametes, and can not, of course, transmit a trait represented by the determiner.

It is evident that six kinds of gametic matings are possible among individuals representing these various formulae. These matings are as follows:

Possible couplings Matings of gametes Product

1. Nulliplex x Nulliplex (aa x aa) == a------a == all nulliplex / / a------a

2. Nulliplex x Simplex (aa x Aa) == a------A == 50 per cent.

/ with character / nulliplex and a------a 50 per cent.

with it simplex.

3. Nulliplex x Duplex (aa x AA) == a------A == all with characters / simplex / a------A

4. Simplex x Simplex (Aa x Aa) == A------A == 25 per cent.

/ with characters / duplex, 50 per a------a cent. with it simplex and 25 per cent. with it nulliplex.

5. Simplex x Duplex (Aa x AA) == A-------A == 50 per cent.

/ with character / duplex and 50 a-------A per cent. with it simplex.

6. Duplex x Duplex (AA x AA) == A-------A == all duplex.

/ / A-------A

=Indications of Incomplete Dominance.--=While in cases of strict Mendelian dominance it is not possible to distinguish directly the simplex from the duplex condition, as a matter of fact the individual of simplex const.i.tution sometimes has the character represented in the single determiner less perfectly developed than in the corresponding character of duplex origin. In studying defects in man due to the absence of a determiner, where theoretically presence of the determiner (normality) is dominant over its absence in individuals of simplex const.i.tution, one finds it recorded with increasing frequency that such individuals are more or less "intermediate" or are "tainted" with the defect; thus showing that the defect though obscured is not wholly in abeyance. Thus individuals carrying epilepsy or feeble-mindedness which are regarded as recessive traits, while not showing specific feeble-mindedness or epilepsy, may nevertheless apparently show a neuropathic taint in the form of migraine, alcoholism or other lapse from normality. The condition is seemingly more akin in some cases to that found in the offspring of certain red flowers crossbred with white flowers, which though red do not show the same intensity of color as the original red parent. Just as here the single determiner or single "dose" of redness is insufficient to produce the intensity of color that appears when the offspring receive two determiners for red, one from each parent, so in man a single determiner for normality of a specific character is inadequate in some cases to make the individual wholly normal. Or possibly some cases are more of the type of those in which the character in question, for instance the red color of some wheats and corn, may be produced by any one of two or three determiners, the intensity of the characters (red color, e. g.) depending on whether one, two or three determiners are present.

=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 individuals both having the character married, and then only in twenty-five per cent. of the offspring (see formula 3). If the trait is a defect all the children showing it, even though marrying normal (nulliplex) individuals, will pa.s.s it on again to half their children, but those who do not show it may ordinarily marry with impunity since its non-expression in their make-up means, as far as we know at present, that their germ-plasm has been purged of the defect and that they are therefore nulliplex with reference to it.

=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 const.i.tutes 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 condition, then one-fourth of children will have blue or gray eyes; for example,

Mating Gametic Product couplings

Pp Pp = P--P = PP, Pp, pP, and pp, or one-fourth / duplex brown, one-half simplex / brown, and one-fourth blue or p--p gray.

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 cla.s.sification 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.

=Hair-Color.--=The inheritance of hair-color has also been the subject of considerable study and while the conditions are not so simple as in the case of eye-color, there is little doubt that it belongs in the Mendelian category. In human hair, color has as its foundation apparently two pigments, black and red. Absence of one or both or various combinations or dilutions of these seemingly account for the prevailing colors in human hair. In general dark hair is dominant to light, although because of the delay sometimes in the darkening of the hair in children this fact is often obscured. Black is dominant to red. People with glossy black hair, according to Davenport, are probably simplex for black, the glossiness being due usually to recessive red. The expectation would be for some of the children of such a pair to have red hair.

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. Summing together a series of recessives Davenport points out that two blue-eyed, flaxen or golden and straight-haired parents will have only children like themselves.

[Ill.u.s.tration: FIG. 21

Diagram showing descent of brachydactyly through five generations; black symbols indicate affected individuals; [male], male; [female], 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 s.e.x 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. This occasional lapse in the appearance of a character when theoretically it should appear is doubtless due in some instances to the fact that what is really inherited is a _tendency_, and although this is present in the apparently normal individual, for some reason the condition itself has not appeared. This might especially be true in the case of a disease which does not manifest itself until late in life. In other cases there are undoubtedly complicating accessory conditions which modify the behavior of the trait somewhat.

OTHER CASES OF DOMINANCE IN MAN