Heterozygote Type Research Articles

Inheritance of High Sugars from Tomato Accession PI 270248 and Environmental Variation between Seasons

Small-fruited cherry tomato accession PI 270248 [Lycopersicon esculentum Mill. var. cerasiforme (Dunal) A. Gray] with high fruit sugars was crossed to large-fruited inbred line Fla.7833-1-1-1 (7833) (L. esculentum) that had normal (low) fruit sugars. The F1 was crossed to PI 270248 and 7833 to obtain BCP1 and BCP2, respectively, and self-pollinated to obtain F2 seed. The resulting population was used to study the inheritance of high sugars from PI 270248. Continuous sugar level frequency distributions of BCP1, BCP2, and F2 suggest that the trait is under polygenic control. Additive variation was significant, but dominance variation was not. There was a heterozygote × heterozygote type of epistasis present that likely caused the F1 sugar level to skew nearly to the level of the high sugar parent. The F2 mean sugar level was lower than the midparent level. Broad-sense heritability was 0.86. There was a significant line × season (fall, spring) interaction where lines with higher sugars were affected more by seasons than lines with lower sugars. Sugar level, in general, was higher in spring. Higher solar radiation in spring than in fall may explain the sugar level difference between the seasons.

Prepared and Application of New Microarray-Based Method for Detecting SNP in the Risk of Hematological Malignancy.

Objective To investigate a new microarray-based method for single nucleotide polymorphisms (SNP) genotyping, and to study the role of 5,10-methylenetetrahydrofolate reductase(MTHFR) SNP in hematological malignancy pathogenesis in the Chinese population.Methods Prepared a aimed gene microarray based on cDNA microarray theory, dual-color fluorescenece hybridization was used for detecting SNP loci, sequencing was performed to confirm the results. In order to prepare the function SNP detection microarray, three different functionalized glass slides were selected, which were modified with 3-aminopropyltriethoxysilane (APTES), poly-l-lysine and glutaraldehyde, respectively. In order to obtain satisfied signal intensity, the ultraviolet crosslinking energy and the immobilized DNA concentration were optimized. By using the above SNP microarray, MTHFR C677T and A1298C SNP loci of 157 controls and 127 patients with hematological malignancy[30 multiple myeloma(MM),28 non-Hodgkin's lymphoma(NHL), 22 acute lymphoblastic leukemia(ALL),40 acute myeloid leukemia(AML),7 chronic myeloid leukemia (CML)] from Jiangsu province were detected.Results Based on the immobilization efficiency, APTES modified glass slides were selected to fabricate DNA microarrays. The optimal ultraviolet crosslinking energy was 400 mJ and the optimal concentration of immobilized DNA was 300 mg/ml. Homozygous wild type, heterozygote type and homozygous mutant type yielded green, yellow and red fluorescence, respectively. Sequencing validated the results.The allele frequencies of MTHFR677C, 677T were 58.7%, 41.3% in patients and 66.9%, 33.1% in controls, respectively; the frequencies of 677CC, 677CT, 677TT genotype were 37.8%, 41.7%, 20.5% in patiens and 45.9%, 42.0%, 12.1% in controls, respectively. The allele frequencies of MTHFR1298A, 1298C were 83.1%, 16.9% in patients and 84.1%, 15.9% in controls, respectively; the frequencies of 1298AA, 1298AC, 1298CC genotype were 70.9%, 24.4%, 4.7% in patiens and 69.4%, 29.3%, 1.3% in controls, respectively. In multivariate analysis, significant difference was observed in the allele frequencies of C677T(χ2=4.08, P=.043) and in the genotype frequency of 677TT(OR 2.09, 95%CI 1.04–4.20, P=.039). The frequencies of 677TT (33.3%) and 1298CC(6.7%) in MM group were found significantly higher than in control group(OR 8.92, 95%CI 1.06–75.24, P=.006; OR=4.80, 95%CI 1.56–14.73, P=.044), resectively. No associations were found between any polymorphisms and susceptibilities to ALL, AML and NHL.Conclusions This microarray-based method is accurate, high-throughput and cheap, suitable for SNP genotyping in a large of individuals. MTHFRC677T polymorphisms influence the risk of hematological malignancy in Chinese population. Both MTHFR677TT and MTHFR1298CC genotype are susceptive to MM.

Adrenomedullin and Vasculitis, Study with Knock Out Mouse

P190 Objectives Adrenomedullin(AM) is not only a potent vasodilator but also regulates several hormone release such as aldosterone, NO and also regulates inflammatory reactions. In order to clarify its physiological role, we generated AM knock-out mouse and investigated its cardiac and vascular changes. Method A point mutation to stop AM translation were induced and by conventional method, AM knock-out mouse was generated. As homozygote was lethal we used heterozygote for this study. In heterozygote plasma and tissue AM level were as half as wild type. Angiotensin II were continuously administered and 8% NaCl diet were loaded to 8 weeks old male heterozygote and wild type for 2 weeks. In some mice, we wrapped silicone tube around the femoral artery and transferred adrenomedullin gene via adenovirus vector topically. Blood pressure were monitored by tail cuff method. After 2 weeks, heart weight were measured and pathological changes were observed. Results Baseline SBP were comparable between heterozygote and wild type (150±10 mmHg vs 142±8 mmHg). One week after angiotensin II and salt loading both mice increased blood pressure to 170±9 mmHg in heterozygote and 168±10 mmHg in wild type. At the end of the study SBP of heterozygote were 160±13 mmHg and that of wild type were 173±9 mmHg. Heart weight/BW were significantly larger in heterozygote (0.0068±0.0003) than in wild (0.0061±0.0002). Perivascular area of coronary artery from heterozygote was full of inflammatory cells and fibrosis. In severe case, coronary aretery showed fibrinoid necrosis. These findings were not found in kidney or other arterioles.The femoral artery from heterozygote showed marked medial proliferation and stenosis compared to wild type. And this change was rescued by AM administration. Conclusion AM is protective against coronary artery injury and cardiomegaly.

Adrenomedullin and Vasculitis, Study with Knock Out Mouse

P190 Objectives Adrenomedullin(AM) is not only a potent vasodilator but also regulates several hormone release such as aldosterone, NO and also regulates inflammatory reactions. In order to clarify its physiological role, we generated AM knock-out mouse and investigated its cardiac and vascular changes. Method A point mutation to stop AM translation were induced and by conventional method, AM knock-out mouse was generated. As homozygote was lethal we used heterozygote for this study. In heterozygote plasma and tissue AM level were as half as wild type. Angiotensin II were continuously administered and 8% NaCl diet were loaded to 8 weeks old male heterozygote and wild type for 2 weeks. In some mice, we wrapped silicone tube around the femoral artery and transferred adrenomedullin gene via adenovirus vector topically. Blood pressure were monitored by tail cuff method. After 2 weeks, heart weight were measured and pathological changes were observed. Results Baseline SBP were comparable between heterozygote and wild type (150±10 mmHg vs 142±8 mmHg). One week after angiotensin II and salt loading both mice increased blood pressure to 170±9 mmHg in heterozygote and 168±10 mmHg in wild type. At the end of the study SBP of heterozygote were 160±13 mmHg and that of wild type were 173±9 mmHg. Heart weight/BW were significantly larger in heterozygote (0.0068±0.0003) than in wild (0.0061±0.0002). Perivascular area of coronary artery from heterozygote was full of inflammatory cells and fibrosis. In severe case, coronary aretery showed fibrinoid necrosis. These findings were not found in kidney or other arterioles.The femoral artery from heterozygote showed marked medial proliferation and stenosis compared to wild type. And this change was rescued by AM administration. Conclusion AM is protective against coronary artery injury and cardiomegaly.

STAGGERED CLINES IN A HYBRID ZONE BETWEEN TWO CHROMOSOME RACES OF THE HARVESTMAN GAGRELLOPSIS NODULIFERA (ARACHNIDA: OPILIONES)

We analyzed a hybrid zone between two chromosome races (2n = 16 and 2n = 22) of a Japanese harvestman, Gagrellopsis nodulifera Sato and Suzuki (Arachnida: Opiliones: Phalangiidae). The hybrid zone is located in the eastern part of Tottori Prefecture, western Honshu. The width of the zone is approximately 5 to 15 km. Three independent tandem fusions/fissions seem to be the main cause of the karyotypic differences between the parental races. Ten karyotypic variants were found in the hybrid zone. They differed by numbers of diploid chromosomes and trivalents detected in meiosis. In most of the collecting sites, karyotypic heterozygotes were less common than expected. A positive correlation was found between number of trivalents in a karyotype and its deficiency rate. In some sites, the deficit of heterozygous individuals was accompanied by an excess of the intermediate homozygotes. One of the three transects across the zone was studied in detail. We found that three types of single heterozygotes (2n = 17, 2n = 19 and 2n = 21) formed a series of successive, spatially separated peaks along the transect. Two types of intermediate homozygotes (2n = 18 and 2n = 20) were also spatially separated. The most parsimonious explanation of such a structure is the staggering of clines of three tandem (or Robertsonian) fusion/fission variants that differentiate the parental races caused by selection against multiple heterozygotes. Analysis of nondisjunction in single heterozygotes demonstrated that there was a strong interindividual variation in nondisjunction rate. The mean frequency of aneuploid MII in single heterozygotes was 0.10 ± 0.03. Crossover exchanges in some critical regions of trivalents result in abnormal chromosomal configurations: chromosomes with unequal chromatids and dicentric chromosomes. Frequency of crossover-induced chromosomal abnormalities was low in single heterozygotes (≃ 4%), and was unexpectedly high in the double heterozygotes (≃ 15%). Selection against karyotypic heterozygotes is considered as a main evolutionary force responsible for the structuring of the hybrid zone. A positive association between diploid chromosome number and altitude was found. The race 2n = 16 tended to occupy lower altitudes than the 2n = 22 parental race. Differences in ecological preferences may be a result of previous adaptations to different environments in allopatry. A hypothesis concerning the origin and evolution of the hybrid zone is proposed.Corresponding Editor: J. Mallet

Effect of bcl-2 deficiency on the radiation response of clonogenic cells in small and large intestine, bone marrow and testis

Purpose : Overexpression of bcl -2 protects against radiation induced apoptosis in lymphohaematopoietic cell types in vivo, whilst bcl -2 deficiency radiosensitizes murine T-lymphocytes in vitro. However, there are few data regarding the influence of bcl-2 deficiency on the radiosensitivity of non-lymphoid cell types. The purpose of this study was to investigate the role of bcl-2 in the clonogenic radiation response of intestinal crypts, bone marrow progenitor cells and testicular stem cells. Method : Survival curves were obtained for each cell type from bcl -2 null (-/-), heterozygote (+/-) and wild type (+/+) mice. Crypt survival in the small and large intestine was assessed using the crypt microcolony assay. Committed haemopoietic progenitors were assayed using in vitro colony-forming cell (CFC) assays and survival of clonogenic spermatogonia was assessed by scoring regenerative tubules at 35 days post-irradiation. Results : There was no difference in small intestine crypt survival between the three genotypes. In the colon, there was a tendency towards lower clonogen survival in the +/- and -/- animals. Haemopoietic in vitro CFC from -/- animals showed lower survival in comparison to +/+ mice, but spermatogonial stem cells were comparatively more radioresistant. Conclusions : Deficiencies in bcl -2 a ffect the radiation response of different cell populations in small but different ways. This may be due to variations between cells in their innate capacity for apoptosis, their dependence on different members of the bcl -2 family gene and their cell-cycle status and p53 expression.

Cancer Risk in ATM Heterozygotes: A Model of Phenotypic and Mechanistic Differences between Missense and Truncating Mutations

The failure to find an increased frequency of ATM mutations in large cancer cohorts, especially breast cancer, is contrary to what was anticipated based on the increased cancer susceptibility of obligate ATM heterozygotes from families with ataxia-telangiectasia (A-T). We hypothesize that this paradox might be resolved if two types of ATM heterozygotes exist and the phenotypes differ, i.e., those with truncating types of mutations (ATMtrunc), that make no protein, and those with missense types of mutations (ATMmis), that make reduced amounts of defective protein. The phenotype of ATMtrunc/trunc mutations is the A-T syndrome; the phenotype of ATMmis/mis mutations, judging from the few homozygous patients that have been documented, appears to include some neurological features and cancer susceptibility but not the A-T syndrome. Evidence is reviewed which suggests that ATMmis/wt mutations are technically more difficult to detect than ATMtrunc/wt mutations. Despite this, most large cancer cohort studies have identified mainly missense mutations and few truncating mutations. This model would require a paradigm shift for cancer risk analyses, to recognize the existence of different allele frequencies for the two types of A-T heterozygotes.

Altered Circadian Period of Locomotor Activity in Carbonic Anhydrase II-Deficient Mice

This study finds lengthened circadian period in a congenic strain of mice homozygous for a null mutation in carbonic anhydrase isoenzyme-II gene on proximal Chromosome 3. Carbonic anhydrase II has the highest turnover rate of any constitutive enzyme. It catalyzes the reversible hydration of carbon dioxide to control intercellular acid/base balance. A strain of congenic mice has a carbonic anhydrase II null mutation within a DBA/2J inbred strain insert on a C57BL/6J inbred strain background. The locomotor activity levels and period of circadian rhythms were examined in the homozygous null mutants and their progenitors, mice heterozygous for the region around the carbonic anhydrase gene. The heterozygous mice siblings and the wild-type siblings served as the controls. During behavioral studies, male and female offspring and parents were housed singly in constant darkness. Locomotor activity was monitored using an infrared photobeam array. Mice homozygous for the carbonic anhydrase null mutation had a longer circadian period than either heterozygote or wild type littermates. Carbonic anhydrase null mutants also had low locomotor activity compared to either heterozygous or wild-type litter mates. This implies that either the physiological changes resulting from absence of carbonic anhydrase II isozyme or the presence of DBA/2J alleles around the carbonic anhydrase locus influence the circadian period and level of locomotor activity in laboratory mice.

Inheritance of a chromosomal polymorphism in odd-year pink salmon from southeastern Alaska

In previous work we found a high frequency of heterozygotes for a fission translocation involving the seventh chromosome pair in odd-year populations of pink salmon (Oncorhynchus gorbuscha) sampled from Washington State to south central Alaska. The populations from southeastern Alaska and northern British Columbia had high frequencies of heterozygotes for a second rearrangement of this same chromosome pair. In these fish one fission product, the larger acrocentric chromosome bearing the nucleolar organizer region (NOR), has undergone an inversion to produce a submetacentric chromosome. In this paper, we present inheritance data on pink salmon from the Gastineau hatchery stock in Juneau, Alaska, where individuals with the two rearrangements are found. Although most of the fish were either homozygous for the normal cytotype or heterozygous for the inversion cytotype, a few individuals heterozygous for the fission cytotype were found. Ten males and ten females were karyotyped, and crosses were set up in all combinations. Individuals with both rearrangements were found in crosses between the two types of heterozygotes, and the ratios of cytotypes in the progeny did not deviate significantly from the expected values. No significant difference in viability of offspring from crosses between individuals with different cytotypes was found up to the age of hatching.Key words: salmon, chromosomal polymorphism, translocation, inversion, cytotype.

Complementation analyses for 45 mutations encompassing the pink-eyed dilution (p) locus of the mouse.

The homozygous and heterozygous phenotypes are described and characterized for 45 new pink-eyed dilution (p) locus mutations, most of them radiation-induced, that affect survival at various stages of mouse development. Cytogenetically detectable aberrations were found in three of the new p mutations (large deletion, inversion, translocation), with band 7C involved in each case. The complementation map developed from the study of 810 types of compound heterozygotes identifies five functional units: jls and jlm (two distinct juvenile-fitness functions, the latter associated with neuromuscular defects), pl-1 and pl-2 (associated with early-postimplantation and preimplantation death, respectively), and nl [neonatal lethality associated with cleft palate (the frequency of rare "escapers" from this defect varied with the genotype)]. Orientation of these units relative to genetic markers is as follows: centromere, Gas-2, pl-1, jls, jlm p, nl (equatable to cp 1 = Gabrb3); pl-2 probably resides in the c-deletion complex. pl-1 does not mask preimplantation lethals between Gas2 and p; and no genes affecting survival are located between p and cp1. The alleles specifying mottling or darker pigment (generically, pm and px, respectively) probably do not represent deletions of p-coding sequences but could be small rearrangements involving proximal regulatory elements.

Efficacy of Marek's disease vaccines in Mhc heterozygous chickens: Mhc congenic x inbred line F1 matings.

The goal of this study is to demonstrate that Mhc (B) heterozygous chickens differ in efficacy of response to several Marek's disease (MD) vaccines. Four types of B2 heterozygotes, in addition to B2B2 homozygotes, were developed by crossing 15.B congenic males to inbred line 7(1) (B2B2) hens. The five types of F1 chicks were intermingled in isolators and vaccinated with one of four types of MD vaccine before inoculation with the very virulent Md5 strain of MD herpesvirus. The F1 chickens differ in development of protective immunity following MD vaccination from two perspectives. First, chickens of a particular Mhc genotype were protected better by some vaccines than others. Second, individual vaccine preparations protected some Mhc genotypes more effectively. We conclude that some MD vaccines are more appropriate than others for certain B-haplotypes when chickens are heterozygous for the Mhc. The value of using Mhc-congenic x inbred line F1 animals for studies concerning the influence of the Mhc on vaccinal immunity is discussed.

Type I Congenital Plasminogen Deficiency Is not a Risk Factor for Thrombosis

The risk of thrombosis in type I congenital plasminogen (PLG) deficiency has been suggested, but is still not confirmed. We studied 40 members of two unrelated families with this disease, and found that 21 were heterozygotes of type I congenital PLG deficiency. Three of them had thrombosis, but the other 18 had no thrombosis. The percentages of family members with no history of thrombosis up to a given age among subjects with type I congenital PLG deficiency and healthy controls were analyzed by the Kaplan-Meier method. No significant difference between the two groups was observed by the generalized Wilcoxon test (p = 0.23). These results suggest that there is no significant correlation between type I congenital PLG deficiency and thrombosis.

Diagnostic and genetic studies in 43 patients with classic cystinuria

Abstract We present results for laboratory screening and diagnostic tests--cyanide-nitroprusside test, semi-quantitative thin-layer chromatography, and quantitative amino acid column chromatography--of 43 patients with classic cystinuria. We report the efficaciousness of the cyanide-nitroprusside test and of thin-layer chromatography, as compared with quantitative amino acid chromatography, for detecting heterozygotes for type II or III cystinuria. The quantitative results for aminoaciduria in 57 blood relatives in 23 families were used to categorize the index patients with classic cystinuria. By column chromatography the ranges of excretion rates (mumol/24 h per 1.73 m2 body surface area) of diagnostic amino acids in the index patients were as follows: cystine 556-54044 (normal 20-128), arginine 131-11543 (10-80), lysine 768-21848 (51-514), ornithine 185-5685 (0-80). Also by column chromatography the median values for arginine and ornithine excretion in cystine-lysinuric heterozygotes (among the 57 blood relatives) were significantly higher (P less than 0.01) than in controls but never approached the values for homozygotes. The cyanide-nitroprusside test results were positive in urine samples of 41 of 43 index patients and in 16 (51.6%) of the urine samples of 31 obligate heterozygotes with column chromatographically proven cystine-lysinuria. Thin-layer chromatography detected all of the homozygotes, all the compound heterozygotes, and 54.8% of the carriers. According to the type of aminoaciduria in their relatives, 11 patients with classic cystinuria could be classified as having classic cystinuria type I, 11 as having type II or III, and three as being compound heterozygotes. We discuss the implications of these results for correct diagnoses and for genetic studies in classic cystinuria.

Diagnostic and genetic studies in 43 patients with classic cystinuria

We present results for laboratory screening and diagnostic tests--cyanide-nitroprusside test, semi-quantitative thin-layer chromatography, and quantitative amino acid column chromatography--of 43 patients with classic cystinuria. We report the efficaciousness of the cyanide-nitroprusside test and of thin-layer chromatography, as compared with quantitative amino acid chromatography, for detecting heterozygotes for type II or III cystinuria. The quantitative results for aminoaciduria in 57 blood relatives in 23 families were used to categorize the index patients with classic cystinuria. By column chromatography the ranges of excretion rates (mumol/24 h per 1.73 m2 body surface area) of diagnostic amino acids in the index patients were as follows: cystine 556-54044 (normal 20-128), arginine 131-11543 (10-80), lysine 768-21848 (51-514), ornithine 185-5685 (0-80). Also by column chromatography the median values for arginine and ornithine excretion in cystine-lysinuric heterozygotes (among the 57 blood relatives) were significantly higher (P less than 0.01) than in controls but never approached the values for homozygotes. The cyanide-nitroprusside test results were positive in urine samples of 41 of 43 index patients and in 16 (51.6%) of the urine samples of 31 obligate heterozygotes with column chromatographically proven cystine-lysinuria. Thin-layer chromatography detected all of the homozygotes, all the compound heterozygotes, and 54.8% of the carriers. According to the type of aminoaciduria in their relatives, 11 patients with classic cystinuria could be classified as having classic cystinuria type I, 11 as having type II or III, and three as being compound heterozygotes. We discuss the implications of these results for correct diagnoses and for genetic studies in classic cystinuria.

身体疾患と脳動脈の硬化

With increase in the elderly population, cerebral atherosclerosis has become one of the major medical problems in Japan, particularly diseases related to cerebral infarction. I report in this paper the relation between cerebrovascular diseases and various vascular factors from clinical as well as pathoanatomical aspects.1) Moderate or severe atherosclerosis appeared as early as in the twenties, thereafter with an increase in the frequency and degree of the pathology in linear form, as shown from results of the nationwide autopsy study sponsored by the Ministry of Education (Chairman: S. Okinaka; Pathologists: Ohtsu, S., et al.).2) The incidence of subjects with severe atherosclerosis in the aorta and middle cerebral artery, increased after 60 years of age, but this tendency was not seen in the coronary and basilar arteries. I call the former the “Living Artery” and the later the “Life Artery”. This distinction may be useful for discussing progression of atherosclerosis of visceral organs.3) More than 50% stenosis on cross-sectioned areas of the internal carotid artery was found in 25% and in the vertebral artery in 23%, in a routine 400 autopsy series of subjects aged 60 years or more; complete occlusion occurred in 2% in the former and in 6% in the latter.4) In diabetics, atherosclerosis of the cervical and intracranial arteries was more pronounced than in non-diabetics. Within the skull, atherosclerosis was more advanced in the posterior circulation in diabetics. The subjects with combined diabetes mellitus, hypercholesterolemia and hypertension almost always showed cerebral infarcts at autopsy. This finding was confirmed by MRI in the clinical level.5) Severe atherosclerosis was significantly frequently distributed in patients with myocardial infarction and/or hypertension. In patients with pulmonary emphysema, malignancy or liver cirrhosis, cerebral atherosclerosis was significantly slighter than in the other diseases, the reasons for which were considered in the discussion.6) In patients showing carotid bruits in their clinical courses, cerebral infarction at autopsy was significantly more frequent than in those without bruits.7) Important risks of cortical type infarction were higher LDL- and lower HDL-cholesterol value than in patients with infarctions in the perforating arterial system. In the latter there was a high risk of hypertension.8) Arteries with advential hyperplasia were common in the infarcted areas of the brain. The pathogenesis of such a secondary change of the arteries was considered in the discussion.9) Familial hypercholesterolemia of the homoor heterozygote type showed a relatively high cerebral infarction on MRI.10) Lp(a) seemed to be a strong indicator for coronary heart disease and cerebral infarction, irrespective of other blood lipid data.11) In patients with vascular dementia, blood pressure should be maintained on more or less higher levels. Greater attention should be paid to the microcirculation of the brain.12) In the future, molecular biological common factors including both atherogenesis and thrombogenesis should be investigated, and special patterns of cerebral circulation should be carefully considered.

Results of newborn screening for galactose metabolic disorders

A screening strategy has been used which uses the Paigen and Beutler methods for the determination of galactose and galactose-1-phosphate. A blood spot test for epimerase has also been developed. In the last 10 years, 265,019 samples from newborns have been tested by these methods. Among the 154 screening positives, we have detected seven cases of epimerase-deficient galactosaemia (Type III), seven cases of Duarte/galactosaemia heterozygotes, 48 cases of other various types of heterozygotes, four cases of persistent hypergalactosaemia, three cases of hepatitis and one case of congenital atresia of the bile duct. These results indicate that our screening system has effectively detected the infants with galactose metabolic disorders.

Inherited Deficiency of the Seventh Component of Complement: Studies of C7‐Consuming Activity

Neither the hemolytic activity nor the protein level of the seventh component of serum complement (C7) was detectable in an 8-year-old girl with nephritis, but in her parents and her brother, they were about half of the normal level. The patient was a homozygote type with a complete deficiency of C7 while her parents and brother were all heterozygote type with a partial deficiency of C7. C7-consuming activity was demonstrated in the native serum of the patient with complete C7 deficiency, and it was found that large amounts of C56 were readily generated upon incubation of the patient's serum with zymosan. It is proposed that the C7-consuming activity in the native serum of this patient is due to small amounts of C56 generated during the activation of serum complement by some kind of infection such as a common cold.

Genetic polymorphisms of orosomucoid ORM1 and ORM2 in Libyans: occurrence of ORM1*2.1 and three new ORM2 alleles.

Genetic polymorphisms of human serum orosomucoid ORM1 and ORM2 gene loci were investigated in a Libyan population sample from Tripoli, n=110, using isoelectric focusing in ultrathin layer polyacrylamide gel containing either Triton X-100 orN-(2-acetamido)-2-aminoethanesulfonic acid (ACES) with subsequent immunofixation. In ORM1 locus, six common phenotypes ORM1 1-1, ORM1 2-1, ORM1 2-2, ORM1 2.1-1, ORM1 2.1-2 and ORM1 3-1 were identified, with allele frequencies as follows:ORM1*1=0.6500,ORM1*2=0.3091,ORM1*2.1=0.0318 andORM1*3=0.0091. In ORM2 locus, one common phenotype ORM2 1 and four new heterozygote types represent products of three new variant alleles tentatively designatedORM2* Tripoli 1, ORM2* Tripoli 2 andORM2*Tripoli 3 were observed. In addition, one subject in which no ORM2 was detectable, the phenotype ORM2 0-0 is suggested. The ORM2 allele frequencies wereORM2*1=0.9816,ORM2*Tripoli 1=0.0092,ORM2*Tripoli 2=0.0046 andORM2*Tripoli 3=0.0046.

THE TRANSPOSABLE ELEMENT Ds AFFECTS THE PATTERN OF INTRAGENIC RECOMBINATION AT THE bz AND R LOCI IN MAIZE

Insertion of the transposable element Ds into either the bz or R locus affects intragenic recombination in various ways. We have examined here one aspect of this problem; namely, the distribution of flanking markers among intragenic recombinations produced by different types of heterozygotes carrying Ds insertion mutations. Heteroallelic combinations of a Ds insertion mutation and a mutation borne on a structurally normal chromosome generate a majority of intragenic recombinants of a crossover type. In contrast to this, most intragenic recombinants obtained from heterozygotes between two different Ds insertion mutations have a parental arrangement of outside markers. Therefore, the resolution of the recombination intermediate would appear to depend on the nature of the mutations in the heterozygote.

Immunoglobulin allotype markers and HLA DR genes in type I diabetes mellitus

Although it is now well established that insulin-dependent (type I) diabetes mellitus is closely associated with genes of the HLA-DR locus, the genetics of the disease remains an area of controversy. It is generally believed that the HLA-linked diabetes genes provide the majority of disease susceptibility to type I diabetes, however, there is some evidence for the existence of other non-HLA-linked genetic loci predisposing to this disorder. Therefore, allotypes of the Gm (immunoglobulin heavy chain) locus on chromosome 14 and of Km (immunoglobulin light chain) locus on chromosome 2 were studied in 180 caucasoid type I diabetic patients. No association between immunoglobulin allotype markers and the whole group of type I diabetes could be observed. However, a particular immunoglobulin allotype, G1m(a), and a particular Gm immunoglobulin phenotype (a−x−f+b+) showed a significant heterogeneity within the diabetics subdivided by HLA-DR type. The data of this study support the concept that (1) the genes in the HLA region provide the majority of, but not the only, genetic susceptibility to type I diabetes mellitus and (2) Gm-associated genes could interact with these susceptibility genes at least in the DR3/4 heterozygote type I diabetics. Further studies should be undertaken in order to elucidate a possible role of these factors in the humoral immune response of type I diabetics and their families.