Simple Recessive Inheritance Research Articles

A SNP of betaine aldehyde dehydrogenase (BADH) enhances an aroma (2-acetyl-1-pyrroline) in sponge gourd (Luffa cylindrica) and ridge gourd (Luffa acutangula)

Luffa is a genus of tropical and subtropical vines belonging to the Cucurbitaceae family. Sponge gourd (Luffa cylindrica) and ridge gourd (Luffa acutangula) are two important species of the genus Luffa and are good sources of human nutrition and herbal medicines. As a vegetable, aromatic luffa is more preferred by consumers than nonaromatic luffa. While the aroma trait is present in the sponge gourd, the trait is not present in the ridge gourd. In this study, we identified Luffa cylindrica’s betaine aldehyde dehydrogenase (LcBADH) as a gene associated with aroma in the sponge gourd based on a de novo assembly of public transcriptome data. A single nucleotide polymorphism (SNP: A > G) was identified in exon 5 of LcBADH, causing an amino acid change from tyrosine to cysteine at position 163, which is important for the formation of the substrate binding pocket of the BADH enzyme. Based on the identified SNP, a TaqMan marker, named AroLuff, was developed and validated in 370 F2 progenies of the sponge gourd. The marker genotypes were perfectly associated with the aroma phenotypes, and the segregation ratios supported Mendelian’s simple recessive inheritance. In addition, we demonstrated the use of the AroLuff marker in the introgression of LcBADH from the aromatic sponge gourd to the ridge gourd to improve aroma through interspecific hybridization. The marker proved to be useful in improving the aroma characteristics of both Luffa species.

Identification and mapping of Mendelian subtypes of disease.

We took as our working hypothesis the premise that there could be a single locus of major effect underlying a subset of cases in the simulated Problem 2 data set, and took as our primary goal the task of mapping that locus. Treating the disease as dichotomous and using discriminant function analysis, we were able to separate affected individuals into two disease categories: Disease Type I (DT-I) cases, whose disease was by hypothesis caused by the major locus; and Disease Type II (DT-II) cases, whose disease was by hypothesis produced by other causes. Segregation analysis showed evidence of simple recessive inheritance among the DT-I individuals. Linkage analysis under the best-fitting recessive model gave clear evidence of linkage to D1G2. In the generating model, this marker is linked to a major gene for disease with recombination fraction theta = 0, and the mode of inheritance at that locus is recessive (when the trait is considered as a dichotomy). We conclude that when the true model is complex, focussing on subtypes of disease that show evidence of simple Mendelian inheritance may be a useful first step in determining the underlying model and mapping major genes.

An epidemiological and genetic study of congenital profound deafness in Tunisia (governorate of Nabeul).

An epidemiological and genetic study of profound deafness has been undertaken in the governorate of Nabeul in Tunisia. This paper deals with sensorineural deafness with no associated abnormalities. The prevalence was estimated to be 0.0007 and four clusters could be identified, two of which represent 51% and 34% respectively of the total number of cases. Segregation analysis performed in 29 pedigrees containing 415 subjects with 129 affected cases provided evidence for simple recessive inheritance with no sporadic cases.

HLA class II DNA genotypes in Graves' disease: clues to inheritance of the HLA-linked component of susceptibility.

Restriction fragment length polymorphism analysis using DQ alpha, DQ beta and DR beta cDNA probes was performed in Graves' disease patients and control subjects. The following restriction fragment patterns were increased in frequency in patients compared with control subjects: 10 + 7.0 + 4.0kb DR beta/TaqI fragments (66% vs 32%; P less than 0.01; corrected P less than 0.06), 7.0 + 4.0kb DQ beta/BamHI fragments (55% vs 15%; P less than 0.001; corrected P less than 0.006), and a DQ alpha/TaqI 4.6kb fragment (75% vs 36%; P less than 0.005; corrected P less than 0.02). These associations could be accounted for by the known association of the B8-DR3 haplotype with the disorder. No non-DR3-related restriction fragment pattern was associated with the disease using any of the probes with restriction enzymes TaqI and BamHI. The 10 + 7.0 + 4.0kb DR beta/TaqI restriction pattern was identified in 23 of 35 Graves' disease patients. All 23 subjects were heterozygous for this pattern. This was inconsistent with simple recessive inheritance of the DR3-associated component of disease susceptibility (P = 0.01). The implications of these findings are discussed with reference to models for the inheritance of the HLA-linked component of Graves' disease susceptibility.

Genetic study on ossification of posterior longitudinal ligament.

Family studies and blood grouping tests were conducted in an attempt to elucidate the etiology and genetic mechanism of ossification of posterior longitudinal ligament of the spine (OPLL). Analysis of the collected date revealed the following results: Testing of inheritance pattern Fitness of OPLL to the hypotheses of simple recessive inheritance, simple dominant inheritance and multifactorial inheritance was tested, but fitness to any one of these hypotheses was statistically denied. Analyses of OPLL and genetic markers A comparative study was made between the OPLL patients and healthy donors residing in Tokyo on the phenotype frequency of the blood groups (eight systems), serum groups (six systems) and red cell enzyme groups (three systems). A significant association of OPLL with MN blood groups, Hp types and PGM1 types was observed. Examination of the correlation after combining MN and Hp showed the coefficient of contingency to be C = 0.6739 and that after the multiple combination of MN, Hp and PGM1 revealed the coefficient of contingency to be C = 0.8923, indicating a remarkably high correlation.

The genetics of Graves' disease: HLA and disease susceptibility.

To relate genetic variation in Graves' disease (GD) susceptibility to polymorphism at MHC loci, clinical and family studies were undertaken in eastern Hungary. Among 1980 relatives of 534 index patients, 2.9% of siblings, 2.7% of offspring, and 3.0% of parents had GD. HLA haplotype combinations in affected sibling pairs were determined in the present data and combined with data in the literature (12 sibling pairs from Farid 1981, 12 from Chan et al. 1980, and 15 from Sasazuki et al. 1983); 43, 23, and 1 affected sibling pairs shared, respectively, 2, 1, and 0 HLA haplotypes. This distribution is inconsistent with simple dominant inheritance, but is consistent with simple recessive inheritance of HLA-related susceptibility over a range of gene frequencies (0.2-0.4). A frequency of 0.3 gives the best fit and is consistent with penetrance of 7.1% for the recessive susceptibility genotype; the data, however, can accommodate penetrance values up to 16%. The distribution of HLA haplotypes in 33 families related disease susceptibility more strongly to DR than to other loci. The distribution of HLA-B8 genotypes in 256 patients was in close agreement with Hardy-Weinberg equilibrium proportions, also favoring recessive inheritance of MHC-related susceptibility. The probability that an individual will be affected with GD can be predicted, based on sex, HLA genotype, and family history. For example, 14.9% of DR3-positive women with an affected first degree relative are likely to be affected. These predictions can be tested as family data accumulate.

Arthrogryposis and Associated Defects in Pigs: Indication of Simple Recessive Inheritance

Arthrogryposis and Associated Defects in Pigs: Indication of Simple Recessive Inheritance

Gene dosage and suceptibility to insulin-dependent diabetes.

1. All members of 33 families in which two or more sibs have insulin-dependent diabetes mellitus (IDDM) were HLA-typed. The results strongly support the hypothesis that, closely linked to the HLA region, there is a locus (S) for susceptibility to IDDM. We use Sd for alleles at this locus which confer susceptibility to disease, and Sa for all other alleles. 2. Published prevalence (recurrence) rates for relatives of an IDDM proband, which are essential for the analysis, are reviewed critically, and a new estimate of prevalence at age 30 in the general population is calculated from published data. 3. The analysis allows for greater risk (penetrance) of the genotype SdSd (two doses of Sd) than of SaSd (one dose of Sd) and for recombination between the HLA region and S. With either our own data on 26 affected sib pairs or a much larger sample assembled by pooling with published data, the maximum-likelihood estimate of the two-dose penetrance is 71%, of the one dose penetrance 6.5%. The hypothesis of differential penetrance according to gene dosage provides a significantly better explanation than either simple dominant or simple recessive inheritance. 4. Estimates of the recombination fraction between HLA and S are very sensitive to the proportion of affected sib pairs sharing neither HLA haplotype, which varies considerably among the samples pooled. With the pooled data the recombination fraction is estimated as 3%, but in view of the strong associations with particular HLA alleles seen in population data, this should probably be considered an upper limit.

Hepatitis--Bs antigen in an isolated Indian population of southern Venezuela: a family study.

A genetic analysis of the presence of HBsAg in a population of which 7.2% of the members were positive is presented. Though the ratios of carriers: non-carriers were generally in good agreement with expectation if the carrier state were determined by homozygosity for a single recessive gene, the two examples of mating most critical to a test of the hypothesis, carrier X carrier, yielded 2 normal children among 4 in one family, and one normal child, the only offspring, in the second family. Other investigators have reported similar findings. We conclude that the hypothesis of simple recessive inheritance cannot be sustained.

Familial nephrotic syndrome

Systematic pedigree information was obtained from 70 patients with idiopathic nephrotic syndrome; 16 patients were found to have familial nephrotic syndrome including 1 pair of affected monozygotic twins, 5 affected sibling pairs, 2 affected first cousins from a consanguineous family and 2 patients with sporadic cases from consanguineous families. Patients with familial and sporadic forms of the disease were compared by applying both clinical and histopathologic criteria. No significant differences were found between these groups, but both had a preponderance of males. In contrast to previous reports, the clinical course in the affected monozygotic twins was quite different, providing evidence for the importance of environmental influences on the course of this disease. Furthermore, in affected relatives neither the clinical course nor histopathologic classification was necessarily similar. The recurrence risk for siblings of patients with idiopathic nephrotic syndrome was 0.06. Several possible modes of inheritance were considered. Segregation analysis permitted the exclusion of simple recessive inheritance. The invariable concordance for the occurrence of nephrotic syndrome in both members of monozygotic twinships as well as the sex ratio renders a mixed model, with a small proportion of high risk recessive cases, equally unlikely. The available data are most consistent with a polygenic model which assumes a continuous distribution of disease liability with a discreet threshold effect.

Odour-Blindness to Musk: Simple Recessive Inheritance

Whissell-Buechy and Amoore1 have reported specific anosmia in humans to two substances, iso-valeric acid and a musk (pentadecalactone), anosmia to the second being inherited as a recessive. They found a difference of incidence in both anosmias between Black and Caucasian subjects.

Letter: Odour-blindness to musk: simple recessive inheritance.

Letter: Odour-blindness to musk: simple recessive inheritance.

7 - Genetics of Coeliac Disease

SUMMARY In conclusion we have obtained confirmation of the familial nature of coeliac disease using adult patients as propositi. The 18·3 per cent frequency of coeliac disease in first-degree relatives is higher than that reported in previous studies which are remarkable in the similarity of their findings (Table 3). It is likely that our higher frequency is due to some selection of relatives for biopsy, for as a group the relatives biopsied tended to have more symptoms and more abnormal blood tests than those who were seen but who did not consent to having a jejunal biopsy. The demonstration of a higher frequency of coeliac disease in families than expected suggests that genetic factors are important in the aetiology of the condition. The concordance for coeliac disease in identical twins, but discordance in dyzygotic twins supports this view as does the lack of any report in the literature of man and wife being affected. In addition, affected parents of a propositus not infrequently have a history of coeliac disease in childhood. However, the possibility does exist that this high familial frequency reflects the action of environmental factors acting in early infancy before gluten is added to the diet as symptoms of gluten sensitivity frequently develop at this time. If acquired factors such as intestinal infection are important in determining subsequent gluten sensitivity then we need to know why only some members of a family are affected while others are not. On the evidence available it does seem that genetic factors are important in determining whether an individual develops coeliac disease and that even if environmental influences are relevant they only modify a genetic predisposition to develop the disease. This study, like others, demonstrates the tendency for affected relatives to appear in each generation and in such numbers as to preclude simple recessive inheritance and suggest a dominant mode of inheritance. However, the findings are not those expected were the disease the expression of the action of a single dominant gene unless there is variable penetrance of such a gene because of the modifying effect of other genes or of environmental factors as yet unknown. Alternatively, the mode of inheritance may be polygenic and this is the conclusion of a number of workers in this field. One genetic marker has been demonstrated amongst the histocompatibility antigens but it is as yet uncertain whether this is the HL-A 8 or the HL-A 1 antigen or the HL-A 1 and 8 haplotype. Sophisticated methods of genetic analysis may clarify this point and perhaps contribute further useful information regarding the inheritance of this disease and assist our understanding of the aetiology of the disorder.

Odour-blindness to musk: simple recessive inheritance.

THREE types of odour-blindness or specific anosmia have been studied, but genetical evidence so far obtained is tentative or inconsistent1. The rare anosmia to the n-butylmercaptan of skunk2, and more commonly the scent of freesia flowers3, may be inherited as autosomal recessive traits. Anosmia to hydrogen cyanide4–6 is complex and its inheritance has not been confirmed7.

Sex-Linked Chocolate Coloration in in the Muscovy Duck

TAIBEL (1961) in Italy reported a brownish mutant color type in the Muscovy duck, Cairina moschata, and gave it the name sepia or faiogeno, with symbol f. Simple recessive inheritance was indicated. In England, “dun” or “brown” Muscovy ducks had been known previously (Appleby, 1949), but apparently no genetic study had been made. A color plate by Peter Scott shows such a color variety in the book “Waterfowl of the World” by Delacour (1964, vol. 4, plate 2).In 1967 I learned that “brown” Muscovies also existed in the eastern part of the U.S., and obtained a trio for breeding tests. I have named the new coloration chocolate, because it is a much richer brown than the recessive “brown-rippled” mutant (Hollander, 1968) and has no ripple markings. Progeny of the original trio were all brown (total 56); also several dead embryos were examined and found to have much less intense.

Die genetischen Probleme der Schizophrenien. Nebst vorläufiger Mitteilung der Ergebnisse in einem Schweizer Isolat (mit 3 Stammbaumskizzen)

SUMMARYThe so-called endogenous psychoses, i. e. the manic-depressive pychosis and the schizophrenias have still to be treated like functional characters, as their probably existing somatic bases are still unknown. It may be granted that these two groups are genetically different, though there are — particularly in isolates — hereditary types of psychoses mixed with both manic-depressive and schizophrenic symptoms. According to the data of twin research, schizophrenias and cyclic psychoses have no common genetic background.The very high concordance of monozygotic twins for schizophrenia is liable to prove the high importance of genetic factors, while it does not exclude accessorial environmental influences in its etiology.A simple recessive inheritance, which seemed to be outruled by most authors, appears now to be possible according to Garrone (1962). Other authors (Slater, Böök) pleaded for irregular dominance of major genes with or without single accessory genes, and others even for an unspecific polygenic origin.The term “ schizoid ” is vague and does not correspond to a satisfactorily clear conception either clinically or genetically. It may be the incomplete expression of a disposition to schizophrenia and more often that of a recessive gene in heterozygotic state or an incompletely dominant gene. Schizoid features which have been observed twice in children with trisomy-22 are not likely to have anything to do with schizophrenic psychoses.Most probably the schizophrenias are heterogenic, but not with regard to clinical variations such as hebephrenia, catatonia, dementia simplex or paranoides. At any rate, we should not rely too much on the empirical hereditary prognosis.The study of the occurrence of schizophrenia in isolates has the advantage that we have to do mostly with one and the same biotype and that we are able to trace the presumable genes throughout 8 and more generations. On the other hand the number of character-bearers is numerically limited.In an isolate of eastern Switzerland with about 400 individuals of a highly inbred and fertile population, the frequency of schizophrenia is at least 1.75%. There are accumulations of the trait in some families and collateral lines. The oldest cases of presumable schizophrenics go back a hundred years; the more recent ones were or are interned in the two Cantonal asylums. The diagnoses in their records were controlled by prominent Swiss psychiatrists. Among the parents and sibs of those schizophrenics only a few can be judged as “ schizoid ” at a psychopathic degree.The parental consanguinity of our propositi is about three times higher than the average of this population, which also contains 3.5% of undifferentiated oligophrenia being low-grade in 1%. The frequency of both schizophrenia and oligophrenia does not account at all for the relatively high number of 5 so-called “ Pfropf-schizophrenias ” (i. e., combinations of schizophrenias with inborn mental deficiency); however, Larsson and Sjögren found the same in a Swedish isolate.While the 14 cases of sure or most probable schizophrenia in our isolate do not clearly show a monomeric recessive inheritance (since Weinberg's sibmethod gives a =10.4% and Bernstein's a priori-method a P = 3.0%), the undifferentiated oligophrenia of all degrees most probably depends on one specific simple recessive gene. It is not unlikely after all that the schizophrenias be inherited in the same way in this population, provided there is a considerably reduced manifestation of a mutated autosomal gene.

Anonychia as a Recessive Autosomal Trait in Man

Anonychia is a rare congenital anomaly. In some reported cases other defects have been associated, and in some there has been a dominant or uncertain mode of inheritance. Recent reviewers have referred to congenital anonychia without other defects as a dominant trait. Cockayne (1) assembled the observations on three small reported kindreds (2, 3, 4) that suggested simple recessive inheritance. There was a total of 5 affected and 13 unaffected siblings, a ratio of 1:2.6. Only the report of Heidingsfeld mentioned consanguinity; in his case the parents were first cousins.

Pattern of hereditary susceptibility in rheumatic fever.

This study is concerned with the pattern of inheritance of susceptibility to rheumatic fever. To investigate the genetic mechanism of inheritance in rheumatic fever the families of a selected parent were brought under observation without regard for the presence or absence of rheumatic fever in the unselected mate or collateral relatives. These data are preferable for genetic analysis since they are not biased by selection of affected children and can therefore be analysed directly by the application of simple Mendelian ratios. Two hundred ninety-one families including 646 siblings were under continuous medical supervision at The New York Hospital for an average period of 10 years. Rheumatic fever occurred in 40 children among a total of 121 offspring in 52 genetically susceptible families. By contrast in 239 nonsusceptible families with a total of 525 children, there were only three children who developed rheumatic fever. Genetic analysis of the data gave good agreement with simple recessive inheritance while excluding other mechanisms. The previous conclusion that susceptibility to rheumatic fever is inherited as a simple recessive trait was corroborated.

HEREDITARY FACTORS IN INFANTILE PROGRESSIVE MUSCULAR ATROPHY

AN OBVIOUS feature of infantile progressive muscular atrophy, as first described by Werdnig 1 and by Hoffmann 2 about fifty years ago, is its familial appearance. This implies that a hereditary factor may play an important part as a cause of the disease. Nevertheless, few attempts have been made to prove this theory and to solve the various genetic problems involved. Using the sibling method of Weinberg to estimate eventual agreement with mendelian laws, Schimkus 3 in 1934 made a calculation on a number of cases collected from earlier publications and concluded from his results that simple recessive inheritance was probable. Schimkus demonstrated that about 25 per cent of all siblings of the primary patients were paralyzed, which was just what he expected to find in case of recessiveness. He did not realize, however, that such ideal figures can be expected only in unselected material. If Schimkus, as I suppose,