The genetic linkage between the PKU locus and the loci for Amylase1, Amylase2, Fy,PGM1, and Rh and the question of assignment of the PKU locus to chromosome No. 1

Summary The alpha-amylase loci Amy₁ and Amy₂ and other loci on chromosome 1 were investigated for their linkage relationship to the PKU locus. Ten families were informative for the study of linkage between PKU/Amy, 20 for PKU-Fy, 11 for PKU/PGM₁, and 10 for PKU/Rh linkage. The probabilities of linkage at different recombinant fractions were calculated according to Bayes' theorem. The results are in striking contrast with those of Kamaryt et al. who found strong evidence for close linkage between the amylase loci and the PKU locus, whereas with our results close linkage can be excluded; loose linkage is possible but unlikely. The results are discussed with regard to the genetic heterogeneity of phenylketonuria.     

Genetic linkage relations of the sixth component of complement (C6)

Summary Linkage relations between the C6 and 33 other genetic marker loci have been analyzed in Norwegian pedigrees, including 114 matings with 388 informative children, by use of the MOSM computer program. No suggestion of linkage was found. Very close or close linkage (<0.06) has been ruled out for males between C6 and the following 19 marker loci: GPT, HLA+Bf, Rh, C3, Hp, PGM ₃, Km, Gm, Fy, Gc, AB0, Jk, GLO ₁, K, MNSs, PTC, ACP ₁, PGM ₁ and Pi. For several of the relations even loose linkage is unlikely.     

Localization of genes on human chromosomes by studies of human-Chinese hamster somatic cell hybrids

Summary About 75 man-Chinese hamster hybrid clones were analysed for their human chromosome complement and simultaneously tested for human enzyme markers. Correlation of the presence of chromosomes and enzyme activity revealed assignments of the PGD linkage group to chromosome 1, ME₁, PGM₃ and IPO-B to 6, LDH-A to 11, LDH-B to 12 and IPO-A to 21.The assignment of PGM₃ puts the HL-A loci on chromosome 6. Segregation of the enzymes of the PGD linkage group was demonstrated in a clone which had retained a deleted chromosome 1. Subclones of this line indicate that the loci for PGD and PGM₁ are situated on the short arm or proximal part of the long arm of 1 and the locus for Pep-C on the long arm.

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Zusammenfassung Etwa 75 Hybrid-Zellklone Mensch/Chinesischer Hamster wurden in bezug auf den menschlichen Anteil ihres Chromosomensatzes analysiert und gleichzeitig auf menschliche Enzym-Marker untersucht. Die Korrelation zwischen Anwesenheit von Chromosomen und Enzym-Markern ließ die Folgerung zu, daß die PGD-Koppelungsgruppe auf Chromosom 1, ME₁, PGM₃ und IPO-B auf Nr. 6, LDH-A auf 11, LDH-B auf 12 und IPO-A auf Chromosom 21 gelegen ist.Die Lokalisation von PGM₃ läßt die Folgerung zu, daß auch die HL-A-loci auf Chromosom 6 lokalisiert sind. Aufspaltung der Enzyme der PGD-Koppelungsgruppe konnte an einem Klon dargestellt werden, der ein deletiertes Chromosom 1 enthielt. Die Subklone dieser Linie zeigen, daß die loci für PGD und PGM₁ auf dem kurzen Arm oder dem proximalen Teil des langen Arms von Chromosom Nr. 1 liegen, während der locus für Pep-C auf dem langen Arm gelegen ist.

     

Possible linkage of HL-A and GLO

Summary In 21 informative families with 60 children, a possible linkage between HL-A and GLO was found (recombination fraction approximatively 0.15). The sequence of the loci on chromosome 6 might be GLO, HL-A, PGM₃, MNSs.

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Zusammenfassung Koppelungsuntersuchungen bei 21 informativen Familien mit 60 Kindern zeigten, daß die Loci HL-A und GLO möglicherweise gekoppelt sind (Rekombinationsfrequenz ca. 15%). Die Reihenfolge der Loci am Chromosom 6 kann wie folgt angenommen werden: GLO, HL-A, PGM₃, MNSs.

     

Analyse der Koppelung zwischen dem HL-A-System und anderen Loci

Zusammenfassung Die Koppelung der HL-A-Gene mit den Loci ABO, Rh, MNSs, P, Fy, Jk, K, SEP, PGM ₁, AK, ADA, GPT, Hp, Gm, Inv, Gc, Pt und Se wurde mit Hilfe der Lod-score-Methode untersucht. Es wurde dabei kein Hinweis für eine enge Koppelung zwischen den HL-A-Loci und den anderen Genorten gefunden.

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Analysis of the linkage between the HL-A loci and the genes of other markers

Summary The linkage of the HL-A genes with the loci ABO, Rh, MNSs, P. Fy, Jk, K, acP, PGM ₁, AK, ADA, GPT, Hp, Gm, Inv, Gc, Pt and ABH secretion was analyses using the lod-score method. There was no evidence for a close linkage between the HL-A loci and the genes of the other markers.

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National Blood Group Reference Laboratory (WHO), National Tissue Typing Reference Laboratory (Council of Europe)     

Localization of the human GLO gene locus

Summary Data on the linkage relation between the GLO locus and the HLA, Bf, and PGM ₃ loci are presented. The family material includes 49 GLO/HLA-B (and/or Bf) segregating matings with 134 children informative on 199 parental meioses. Of phase-known meioses, 3 are recombinants and 75 nonrecombinants; linkage is therefore proven. From the total material a distance of 2.5 cM between GLO and HLA-B/Bf is calculated; and from the segregation in some informative family groups it is shown that GLO is situated between PGM ₃ and HLA-B/Bf.     

Adenosine deaminase polymorphism (EC: 3.5.4.4): Formal genetics and linkage relations

Summary The formal genetics of the ADA polymorphism had been investigated in a series of 156 German families with 319 children. The results correspond to the formal model of two alleles at an autosomal locus. There is no evidence for close linkage between the loci of ADA and ABO, MNS, Kell, P, Duffy, Rhesus, Haptoglobin, Gc, ac. Phosphatase, AK, PGM₁, 6-PGD.Supported by the Deutsche Forschungsgemeinschaft.     

Chromosome localization and gene synteny of the major histocompatibility complex in the owl monkey,Aotus

Rodent cells were hybridized with owl monkey (Aotus) cells of karyotypes II, III, V, and VI. Aotus-rodent somatic hybrid lines preferentially segregating Aotus chromosomes were selected to determine the chromosomal location of the major histocompatibility complex and other genes with which it is syntenic in man. Based on correlation between concordant segregation of the chromosome as visualized by G-banding and expression of the Aotus antigens or enzymes in independent Aotus-rodent hybrid clones, we have assigned Aotus gene loci for the MHC, GLO, ME₁, SOD₂, and PGM₃ to Aotus chromosome 9 of karyotype VI (2n=49/50), chromosome 10 of karyotype V (2n=46), and chromosome 7 of karyotypes II and III (2n = 54 and 53). On the basis of banding patterns we previously postulated that these chromosomes of the different karyotypes were homologous. The gene assignments reported here provide independent evidence for that hypothesis. Aotus chromosomes 9 (K-VI), 10 (K-V), and 7 (K-II, III) are homologous to human chromosome 6 in that they all code for the MHC, GLO, ME₁, SOD₂, and PGM₃. The structural differences between these homologous chromosomes probably resulted from a pericentric inversion.Abbreviations used in this paper MHC major histocompatibility complex - HLA human lymphocyte antigen - PGM3 phosphoglucomutase-3 - ME₁ cytoplasmic malic enzyme-1 - SOD₂ superoxide dismutase-B - GLO glyoxalase 1 - OMLA owl monkey leukocyte antigens - K karyotype - ₂-M ₂-microglobulin - DMEM Dulbecco's modification of Eagle's medium - PEG polyethylene glycol - HAT hypoxanthine, aminopterin, and thymidine - KC1 potassium chloride - G-band-trypsin Giemsa band     

Substrate affinity in PGM1, PGM2, and PGM3 isozymes

Summary An easy method for routine detection of PGM₁, PGM₂, and PGM₃ isozymes is given. Differences in substrate affinity are discussed. Gene products pgm₁ can be differentiated from gene products pgm₃ by cofactor requirement.     

Polymorphic Analysis of the Human Phosphoglucomutase-3 Gene Based on Mismatched PCR–RFLP Technique

Polymorphic analysis of human phosphoglucomutase-3 (PGM₃) has been carried out from the level of the gene product. Due to a weak zymogram, leading to ambiguity in phenotyping, information on the PGM ₃ locus has rarely been reported. In this study, the missense mutation G1396A, confirmed to underlie common phenotypes of PGM₃, was identified by performing mismatched PCR–RFLP. Population data on the PGM ₃ locus was also obtained for the first time in China. The allele frequency distribution was PGM ₃ *1 = 0.625, PGM ₃ * 2 = 0.375, and no deviation from Hardy–Weinberg equilibrium was observed. The application of the information in both genetics and forensic medicine demonstrated that the polymorphism information content was 0.5163, heterozygosity 0.4872, power of discrimination 0.5986, and probability of paternity exclusion 0.1794. Polymorphic analysis of the locus at the DNA level will also provide significant data for disease susceptibility and linkage analysis.     

Human phosphoglycolate phosphatase (PGP) E.C.3.1.3.18: Linkage analysis

Summary Linkage data on phosphoglycolate phosphatase (PGP) E.C.3.1.3.18 and 26 other human genetic markers are presented. One hundred and one families from the southwestern area of Germany were tested. Close linkage between PGP and the following markers could be ruled out: AB0, acP, ADA, GPT, PGM₁, GLO, HLA, and PGM₃. There is some evidence for possible linkage with MNSs, Rh, Gm and EsD. Family segregation data confirm the hypothesis formerly established by Barker and Hopkinson: three common alleles PGP¹, PGP² and PGP³ at an autosomal locus PGP.Supported by the Deutsche ForschungsgemeinschaftSupported by DAAD and Portuguese Inst. for Scientific Research (INIC)     

An improved method of typing hair sheath cells using the PGM3 locus following starch gel electrophoresis

Summary The PGM₃ locus, like the PGM₁ locus, is shown to be easily demonstrated in hair sheath cells using starch gel electrophoresis. The discriminating power of the total system (PGM₁ and PGM₃) on starch gel electrophoresis closely approaches that observed by isoelectric focusing of the PGM₁ locus. Family studies of the PGM₃ locus variants in hair sheath cells confirm that the alleles responsible are inherited in a Mendelian fashion independent of the PGM₁ locus.     

Aminolevulinate dehydratase (E.C. 4.2.1.24): Linkage analysis

Summary Linkage data on aminolevulinate dehydratase (ALADH, E.C. 4.2.1.24) and a series of other human genetic markers are presented. One hundred and two families (25 of them being informative) from southwestern Germany were tested. Close linkage (=0.05) between ALADH and the following markers could be excluded: Rh, PGM₁, Fy, ACP1, MNSs, HLA, Bf, GLO, PGM₃, Jk, Pi, PGP, K, GPT. There is some evidence of possible linkage with HPA.     

A high‐resolution radiation hybrid map of the river buffalo major histocompatibility complex and comparison with BoLA

The major histocompatibility complex (MHC) in mammals codes for antigen‐presenting proteins. For this reason, the MHC is of great importance for immune function and animal health. Previous studies revealed this gene‐dense and polymorphic region in river buffalo to be on the short arm of chromosome 2, which is homologous to cattle chromosome 23. Using cattle‐derived STS markers and a river buffalo radiation hybrid (RH) panel (BBURH₅₀₀₀), we generated a high‐resolution RH map of the river buffalo MHC region. The buffalo MHC RH map (cR₅₀₀₀) was aligned with the cattle MHC RH map (cR₁₂₀₀₀) to compare gene order. The buffalo MHC had similar organization to the cattle MHC, with class II genes distributed in two segments, class IIa and class IIb. Class IIa was closely associated with the class I and class III regions, and class IIb was a separate cluster. A total of 53 markers were distributed into two linkage groups based on a two‐point LOD score threshold of ≥8. The first linkage group included 32 markers from class IIa, class I and class III. The second linkage group included 21 markers from class IIb. Bacterial artificial chromosome clones for seven loci were mapped by fluorescence in situ hybridization on metaphase chromosomes using single‐ and double‐color hybridizations. The order of cytogenetically mapped markers in the region corroborated the physical order of markers obtained from the RH map and served as anchor points to align and orient the linkage groups.     

Investigation of PGM13, PGM16, and PGM17 variants by isoelectric focussing. Evidence for new subtypes of the PGM 1 3 and PGM 1 7 alleles

Summary A total of 345 haemolysates previously phenotyped by starch gel electrophoresis and known to contain the products of the PGM ₁ ³ , PGM ₁ ⁶ , and PGM ₁ ⁷ alleles have been analyzed by thin layer polyacrylamide gel isoelectric focussing in the pH range 5–7. Two common subtypes, 3+and 3-, of the PGM ₁ ³ allele have been found in a number of Pacific populations. A single form of the PGM ₁ ⁷ allele was observed in the Western Caroline Islands. In contrast, one of two Indian PGM₁7 variants focussed to a different position when compared with the form found at polymorphic frequency in the Western Caroline Islands. Only one type of the PGM ₁ ⁶ allele was detected during the present investigation.     

Genetic Variation of Microsatellite Loci in the Major Histocompatibility Complex (MHC) Region in the Southeast Asian House Mouse (<Emphasis Type="Italic">Mus musculus castaneus</Emphasis>)

Major histocompatibility complex (MHC) genes are the most polymorphic loci known for vertebrates. Here we employed five microsatellite loci closely linked to the MHC region in an attempt to study the amount of genetic variation in 19 populations of the southeast Asian house mouse (Mus musculus castaneus) in Taiwan. The overall polymorphism at the five loci was high (H_e = 0.713), and the level of polymorphism varied from locus to locus. Furthermore, in order to investigate if selection is operating on MHC genes in natural mouse populations, we compared the extent and pattern of genetic variation for the MHC-linked microsatellite loci (the MHC loci) with those for the microsatellite loci located outside the MHC region (the non-MHC loci). The number of alleles and the logarithm of variance in repeat number were significantly higher for the MHC loci than for the non-MHC loci, presumably reflecting linkage to a locus under balancing selection. Although three statistical tests used do not provide support for selection, their lack of support may be due to low statistical power of the tests, to weakness of selection, or to a profound effect of genetic drift reducing the signature of balancing selection. Our results also suggested that the populations in the central and the southwestern regions of Taiwan might be one part of a metapopulation structure.     

Rare phenotypes of the phosphoglucomutase locus 1 detectable by isoelectric focusing on Cellogel

Summary The rare phenotypes PGM₁, determined by alleles PGM ₃ ¹ , PGM ₄ ¹ , PGM ₆ ¹ , and PGM ₇ ¹ were examined by starch gel electrophoresis and cellulose acetate gel isoelectric focusing and were compared with the commonest phenotypes of PGM₁.The frequencies of the rare genes found in the Polish populations were as follows: in Lublin, PGM ₃ ¹ =0.0002, PGM ₄ ¹ =0.0005, PGM ₆ ¹ =0.0010, and PGM ₇ ¹ =0.0005; in Wroclaw, PGM ₃ ¹ =0.0000, PGM ₄ ¹ =0.0005, PGM ₆ ¹ =0.0007, and PGM ₇ ¹ =0.0002.The results suggest that the F and S type variants of the genes PGM ₄ ¹ and PGM ₇ ¹ probably do not occur. It is still possibile that F and S variants exist for the genes PGM ₃ ¹ and PGM ₆ ¹ .     

Linkage analysis of HSP70 genes and historecognition locus in Botryllus schlosseri

 The protochordate allorecognition system has long invited comparison with the vertebrate major histocompatibility complex (MHC). In the colonial species Botryllus schlosseri, a rapid fusion or rejection response resembling graft acceptance or rejection in vertebrates is controlled by a single highly polymorphic genetic region. Because linkage between heat shock protein 70 (HSP70) genes and the MHC appears to be conserved within the vertebrate lineage, linkage relationships between two HSP70 genes (HSP70.1 and HSP70.2) and the historecognition locus (FuHC) have been analyzed in B. schlosseri. Segregation patterns of restriction fragment length polymorphisms located in the 3′ flanking regions of HSP70.1 and HSP70.2 were determined for progeny of defined crosses. These progeny were also analyzed for fusibility type by an in vivo cut colony assay. No close linkage was detected between any of the three loci. These results do not support the hypothesis that the allorecognition response in B. schlosseri is determined by an MHC homologue. However, it remains a possibility that orthologues of other MHC-linked genes will be linked to the B. schlosseri FuHC. Received: 29 June 1997 / Revised: 6 October 1997     

Estimation of number and size of QTL effects in forest tree traits

Mapping the genetic architecture of forest tree traits is important in order to understand the evolutionary forces that have shaped these traits and to facilitate the development of genomic-based breeding strategies. We examined the number, size, and distribution of allelic effects influencing eight types of traits using 30 published mapping studies (linkage and association mapping) in forest trees. The sizes of allelic effects, measured as the phenotypic variance explained, generally showed a severely right-skewed distribution. We estimated the numbers of underlying causal effects (n _qtl ) for different trait categories by improving a method previously developed by Otto and Jones (Genetics 156:2093–2107, 2000). Estimates of n _qtl based on association mapping studies were generally higher (median at 643) than those based on linkage mapping (median at 33). Comparisons with simulated linkage and association mapping data suggested that the lower n _qtl estimates for the linkage mapping studies could partly be explained by fewer causal loci segregating within the full-sib family populations normally used, but also by the cosegregation of causal loci due to limited recombination. Disease resistance estimates based on linkage mapping studies had the lowest median of four underlying effects, while growth traits based on association mapping had about 580 effects. Theoretically, the capture of 50% of the genetic variation would thus require a population size of about 200 for disease resistance in linkage mapping, while growth traits in association mapping would require about 25,000. The adequacy and reliability of the improved method was successfully verified by applying it to the simulated data.     

RAPD linkage mapping in a longleaf pine x slash pine F1 family

Random amplified polymorphic DNAs (RAPDs) were used to construct linkage maps of the parent of a longleaf pine (Pinus palustris Mill.) slash pine (Pinus elliottii Englm.) F₁ family. A total of 247 segregating loci [233 (1∶1), 14 (3∶1)] and 87 polymorphic (between parents), but non-segregating, loci were identified. The 233 loci segregating 1∶1 (testcross configuration) were used to construct parent-specific linkage maps, 132 for the longleaf-pine parent and 101 for the slash-pine parent. The resulting linkage maps consisted of 122 marker loci in 18 groups (three or more loci) and three pairs (1367.5 cM) for longleaf pine, and 91 marker loci in 13 groups and six pairs for slash pine (952.9 cM). Genome size estimates based on two-point linkage data ranged from 2348 to 2392 cM for longleaf pine, and from 2292 to 2372 cM for slash pine. Linkage of 3∶1 loci to testcross loci in each of the parental maps was used to infer further linkages within maps, as well as potentially homologous counterparts between maps. Three of the longleaf-pine linkage groups appear to be potentially homologous counterparts to four different slash-pine linkage groups. The number of heterozygous loci (previously testcross in parents) per F₁ individual, ranged from 96 to 130. With the 87 polymorphic, but non-segregating, loci that should also be heterozygous in the F₁ progeny, a maximum of 183–217 heterozygous loci could be available for mapping early height growth (EHG) loci and for applying genomic selection in backcross populations.