The evidence available from pedigrees has revealed the simplest form of Mendelian inheritance in several human defects and diseases, among which may be mentioned presenile cataract of the eyes, an abnormal form of skin thickening in the palms of the hands and soles of the feet, known as tylosis, and epidermolysis bullosa, a disease in which the skin rises up into numerous bursting blisters.
Among the most interesting of all human pedigrees is one recently built up by Mr. Nettleship from the records of a night-blind family living near Monpelier in the south of France. In night-blind people the retina is insensitive to light which falls below a certain intensity, and such people are consequently blind in failing daylight or in moonlight. As the Monpelier case had excited interest for some time, the records are unusually complete. They commence with a certain Jean Nougaret, who was born in 1637, and suffered from night-blindness, and they end for the present with children who are to-day but a few years of age. Particulars are known of over 2000 of the descendants of Jean Nougaret. Through ten generations and nearly three centuries the affection has behaved as a Mendelian dominant, and there is no sign that long-continued marriage with folk of normal vision has produced any amelioration of the night-blind state.
Pedigree of a hæmophilic family. Affected (all males) represented by black, and normals of both sexes by light circles. (From Stahel.)
Besides cases such as these where a simple form of Mendelian inheritance is obviously indicated, there are others which are more difficult to read. Of some it may be said that on the whole the peculiarity behaves as though it were an ordinary dominant; but that exceptions occur in which affected children are born to unaffected parents. It is not impossible that the condition may, like colour in the sweet pea, depend upon the presence or absence of more than one factor. In none of these cases, however, are the data sufficient for determining with certainty whether this is so or not.
A group of cases of exceptional interest is that in which the incidence of disease is largely, if not absolutely, restricted to one sex, and so far as is hitherto known the burden is invariably borne by the male. In the inheritance of colour-blindness (p. [117]) we have already discussed an instance in which the defect is rare, though not
unknown, in the female. Sex-limited inheritance of a similar nature is known for one or two ocular defects, and for several diseases of the nervous system. In the peculiarly male disease known as hæmophilia the blood refuses to clot when shed, and there is nothing to prevent great loss from even a superficial scratch. In its general trend the inheritance of hæmophilia is not unlike that of horns among sheep, and it is possible that we are here again dealing with a character which is dominant in one sex and recessive in the other. But the evidence so far collected points to a difference somewhere, for in hæmophilic families the affected males, instead of being equal in number to the unaffected, show a considerable preponderance. The unfortunate nature of the defect, however, forces us to rely for our interpretation almost entirely upon the families produced by the unaffected females who can transmit it. Our knowledge of the offspring of "bleeding" males is as yet far too scanty, and until it is improved, or until we can find some parallel case in animals or plants, the precise scheme of inheritance for hæmophilia must remain undecided.
Though by far the greater part of the human evidence relates to abnormal or diseased conditions, a start has been made in obtaining pedigrees of normal characters. From the ease with which it can be observed, it was natural that eye-colour should be early selected as a subject of investigation, and the work of Hurst and others
has clearly demonstrated the existence of one Mendelian factor in operation here. Eyes are of many colours, and the colour depends upon the pigment in the iris. Some eyes have pigment on both sides of the iris—on the side that faces the retina as well as on the side that looks out upon the world. Other eyes have pigment on the retinal side only. To this class belong the blues and clear greys; while the eyes with pigment in front of the iris also are brown, hazel, or green in various shades according to the amount of pigment present. In albino animals the pigment is entirely absent, and as the little blood-vessels are not obscured the iris takes on its characteristic pinkish-red appearance. The condition in which pigment is present in front of the iris is dominant to that in which it is absent. Greens, browns, or hazels mated together may, if heterozygous, give the recessive blue, but no individuals of the brown class are to be looked for among the offspring of blues mated together. The blues, however, may carry factors which are capable of modifying the brown. Just as the pale pink-tinged sweet pea (Pl. IV., 9) when mated with a suitable white gives only deep purples, so an eye with very little brown pigment mated with certain blues produces progeny of a deep brown, far darker than either parent. The blue may carry a factor which brings about intensification of the brown pigment. There are doubtless other factors which modify the brown when present, but we do not yet know enough of the