SUMMARY We sequenced all protein-coding regions of the genome (the “exome”) in two family members with combined hypolipidemia, marked by extremely low plasma levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. These two participants were compound heterozygotes for two distinct nonsense mutations in ANGPTL3 (encoding the angiopoietin-like 3 protein). ANGPTL3 has been reported to inhibit lipoprotein lipase and endothelial lipase, thereby increasing plasma triglyceride and HDL cholesterol levels in rodents. Our finding of ANGPTL3 mutations highlights a role for the gene in LDL cholesterol metabolism in humans and shows the usefulness of exome sequencing for identification of novel genetic causes of inherited disorders. (Funded by the National Human Genome Research Institute and others.)

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Familial hypobetalipoproteinemia (FHBL), an autosomal dominant disorder, is defined as <5th percentile LDL-cholesterol or apolipoprotein (apo) B in the plasma. FHBL subjects are generally heterozygous and asymptomatic. Three genetic forms exist: (i) premature stop codon specifying mutations of APOB; (ii) FHBL linked to a susceptibility locus on the chromosome 3p21; and (iii) FHBL linked neither to APOB nor to the chromosome 3p21. In heterozygous apoB-defective FHBL, the hepatic VLDL export system is defective because apoB 100, the product of the normal allele, is produced at approximately 25% of normal rate, and truncated apoB is cleared too rapidly. The reduced capacity for hepatic triglyceride export increases hepatic fat three-fold. Indexes of adiposity and insulin action are similar to controls. 'Knock-in' mouse models of apoB truncations resemble human FHBL phenotypes. Liver fat in the chromosome 3p21-linked FHBL is normal. Elucidation of the genetic basis of the non-apoB FHBL could uncover attractive targets for lipid-lowering therapy. (See note added in proof.).

Background & Aims-Hepatic steatosis is associated with insulin resistance, but it is not clear whether increased intrahepatic triglyceride (IHTG) content causes the resistance or is a marker. Subjects with familial hypobetalipoproteinemia (FHBL) have high levels of IHTG because of a genetic defect in hepatic export of triglycerides, and provide a unique cohort to study the relationship between steatosis and insulin sensitivity.

Breeding soybean [Glycine max (L.) Merr.] cultivars for resistance to soybean cyst nematode (SCN) [Heterodera glycines Ichinohe] is the most efficient means to control this pest. Evaluating and developing new resistance germplasm sources for soybean breeding is very important to prevent SCN from race shifts and provide durable resistance in soybean. We evaluated a newly found germplasm, soybean plant introduction (PI) 89772, which is resistant to SCN Races 1, 2, 3, 5, and moderately resistant to Race 14. The objectives were to identify molecular markers associated with SCN resistance, investigate resistant allelic relationships, and evaluate marker‐assisted selection efficiency. The F2 and F2:3 populations were produced by crossing PI 89772 with the susceptible soybean cultivar Hamilton. Thirty‐nine restriction fragment length polymorphism (RFLP) and 54 simple sequence repeat (SSR) markers found to be polymorphic were used to anchor loci conferring resistance to SCN Races 1, 2, 3, and 5. Two to three loci were found to give resistance to each SCN race. We found that resistance loci for different races could be anchored within the same region on linkage group (LG) G. A region on LG B1 was also shared by loci providing resistance to SCN Races 1, 2, and 5. Our results indicated that no single locus could provide complete resistance to any one SCN race. The major loci combinations provided high levels of resistance. We conclude that these markers could be highly useful in marker‐assisted selection.